Jane Salodof MacNeil

The role of bevacizumab has been among the more contentious issues in breast cancer oncology of late. At the San Antonio Breast Cancer Symposium, investigators will add results from two more trials – the BEATRICE and LEA studies – to the ongoing debate.

BEATRICE Targets Early Triple-Negative Disease

Patients had to have confirmed triple-negative disease to be enrolled in the multinational, randomized, open-label BEATRICE study sponsored by Hoffman-La Roche, which markets bevacizumab (Avastin) in Europe.

Their tumors had to be operable primary invasive breast cancer, for which the patients completed definitive locoregional surgery. Those with locally advanced breast cancer were excluded from BEATRICE, which had a target enrollment of more than 2,500 patients.

The underlying question is whether adding 1 year of bevacizumab to standard adjuvant therapy is safe and can improve efficacy. Invasive disease–free survival is the primary outcome measure of BEATRICE, which began recruitment in 2007. "Primary" results are slated for presentation in General Session 6 at the San Antonio meeting (S6-5). Investigators also have prepared a biomarker analysis (Poster session 3, P3-06-34).

LEA Focuses on Advanced Hormone Receptor–Positive Disease

The first efficacy results from the phase III LEA study will focus on the addition of bevacizumab to first-line endocrine treatment in women who are eligible for hormonal therapy and also HER2 negative.

The Spanish Breast Cancer Research Group sponsored the trial in collaboration with the German Breast Group and Hoffmann-La Roche. It was designed to test the hypothesis that targeting the vascular endothelial growth factor (VEGF) with bevacizumab could present resistance to endocrine therapy "in patients with advanced breast cancer sensitive to such treatment" (Cancer Res. 2011;71(24 Supplement):OT3-01-15 [doi: 10.1158/0008-5472.SABCS11-OT3-01-15]).

The protocol called for enrollment of 378 patients with locally advanced or metastatic breast cancer. All received endocrine therapy with letrozole (Femara) or fulvestrant (Faslodex) during the trial; the experimental arm also received bevacizumab, and patients could continue on bevacizumab if they had not progressed on study.

Two-year progression-free survival is the primary end point of the trial, which began recruitment in November 2007. The first efficacy results will be presented in San Antonio (General session 1, S1-7).

Ongoing Quest to Define Who Would Benefit

Just over a year ago, on Nov. 18, 2011, Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced her decision to revoke an indication for bevacizumab in combination with paclitaxel for metastatic breast cancer. She acted after an emotional public hearing at which women with stage IV disease testified that they benefited from bevacizumab.

Earlier, the Oncologic Drugs Advisory Committee (ODAC) had voted unanimously in favor of withdrawal, citing toxicity and noting that confirmatory trials had not repeated the magnitude of benefit in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) on which accelerated approval had been based.

The National Comprehensive Cancer Network (NCCN) has stood by its endorsement of bevacizumab in combination with paclitaxel, however. "The data observed in the [E2100 trial] really had not changed from its approval previously, and we thought that if the data were compelling 2 years ago, why isn’t it compelling enough today?" explained Dr. Robert W. Carlson of Stanford (Calif.) University, chair of the NCCN’s breast cancer panel, after the FDA moved to revoke the indication.

Genentech, the U.S. drugmaker owned by Roche, expressed disappointment with the final FDA decision, and vowed to continue seeking biomarkers that would identify which breast cancer patients can benefit from bevacizumab.

This fall, investigators presented results of the Roche-sponsored TURANDOT trial at the annual meeting of the European Society for Medical Oncology in Vienna. They reported that paclitaxel appeared to be a better partner than capecitabine (Xeloda) for bevacizumab in patients with metastatic breast cancer, but overall survival was not significantly different between the two combinations, and results echoed outcomes in earlier trials.

Quality-of-life results from the TURANDOT trial will be presented in a poster session in San Antonio (Poster session, P5-17-03). Among the other scheduled bevacizumab presentations are:

• Final results of the single-arm, phase II AVANTHER trial from Spain. Investigators combined bevacizumab and trastuzumab (Herceptin) with weekly paclitaxel as a neoadjuvant treatment in HER2-positive breast cancer. Treatment was followed by surgery and adjuvant therapy (Poster session 1, P1-14-10).

• First toxicity results from the Eastern Cooperative Oncology Group E5103 trial. This randomized phase III study compared doxorubicin, cyclophosphamide, and paclitaxel with and without bevacizumab in patients with lymph node–positive or high-risk, lymph node–negative breast cancer (Poster session 5, P5-17-01).

The role of bevacizumab has been among the more contentious issues in breast cancer oncology of late. At the San Antonio Breast Cancer Symposium, investigators will add results from two more trials – the BEATRICE and LEA studies – to the ongoing debate.

BEATRICE Targets Early Triple-Negative Disease

Patients had to have confirmed triple-negative disease to be enrolled in the multinational, randomized, open-label BEATRICE study sponsored by Hoffman-La Roche, which markets bevacizumab (Avastin) in Europe.

Their tumors had to be operable primary invasive breast cancer, for which the patients completed definitive locoregional surgery. Those with locally advanced breast cancer were excluded from BEATRICE, which had a target enrollment of more than 2,500 patients.

The underlying question is whether adding 1 year of bevacizumab to standard adjuvant therapy is safe and can improve efficacy. Invasive disease–free survival is the primary outcome measure of BEATRICE, which began recruitment in 2007. "Primary" results are slated for presentation in General Session 6 at the San Antonio meeting (S6-5). Investigators also have prepared a biomarker analysis (Poster session 3, P3-06-34).

LEA Focuses on Advanced Hormone Receptor–Positive Disease

The first efficacy results from the phase III LEA study will focus on the addition of bevacizumab to first-line endocrine treatment in women who are eligible for hormonal therapy and also HER2 negative.

The Spanish Breast Cancer Research Group sponsored the trial in collaboration with the German Breast Group and Hoffmann-La Roche. It was designed to test the hypothesis that targeting the vascular endothelial growth factor (VEGF) with bevacizumab could present resistance to endocrine therapy "in patients with advanced breast cancer sensitive to such treatment" (Cancer Res. 2011;71(24 Supplement):OT3-01-15 [doi: 10.1158/0008-5472.SABCS11-OT3-01-15]).

The protocol called for enrollment of 378 patients with locally advanced or metastatic breast cancer. All received endocrine therapy with letrozole (Femara) or fulvestrant (Faslodex) during the trial; the experimental arm also received bevacizumab, and patients could continue on bevacizumab if they had not progressed on study.

Two-year progression-free survival is the primary end point of the trial, which began recruitment in November 2007. The first efficacy results will be presented in San Antonio (General session 1, S1-7).

Ongoing Quest to Define Who Would Benefit

Just over a year ago, on Nov. 18, 2011, Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced her decision to revoke an indication for bevacizumab in combination with paclitaxel for metastatic breast cancer. She acted after an emotional public hearing at which women with stage IV disease testified that they benefited from bevacizumab.

Earlier, the Oncologic Drugs Advisory Committee (ODAC) had voted unanimously in favor of withdrawal, citing toxicity and noting that confirmatory trials had not repeated the magnitude of benefit in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) on which accelerated approval had been based.

The National Comprehensive Cancer Network (NCCN) has stood by its endorsement of bevacizumab in combination with paclitaxel, however. "The data observed in the [E2100 trial] really had not changed from its approval previously, and we thought that if the data were compelling 2 years ago, why isn’t it compelling enough today?" explained Dr. Robert W. Carlson of Stanford (Calif.) University, chair of the NCCN’s breast cancer panel, after the FDA moved to revoke the indication.

Genentech, the U.S. drugmaker owned by Roche, expressed disappointment with the final FDA decision, and vowed to continue seeking biomarkers that would identify which breast cancer patients can benefit from bevacizumab.

This fall, investigators presented results of the Roche-sponsored TURANDOT trial at the annual meeting of the European Society for Medical Oncology in Vienna. They reported that paclitaxel appeared to be a better partner than capecitabine (Xeloda) for bevacizumab in patients with metastatic breast cancer, but overall survival was not significantly different between the two combinations, and results echoed outcomes in earlier trials.

Quality-of-life results from the TURANDOT trial will be presented in a poster session in San Antonio (Poster session, P5-17-03). Among the other scheduled bevacizumab presentations are:

• Final results of the single-arm, phase II AVANTHER trial from Spain. Investigators combined bevacizumab and trastuzumab (Herceptin) with weekly paclitaxel as a neoadjuvant treatment in HER2-positive breast cancer. Treatment was followed by surgery and adjuvant therapy (Poster session 1, P1-14-10).

• First toxicity results from the Eastern Cooperative Oncology Group E5103 trial. This randomized phase III study compared doxorubicin, cyclophosphamide, and paclitaxel with and without bevacizumab in patients with lymph node–positive or high-risk, lymph node–negative breast cancer (Poster session 5, P5-17-01).

The role of bevacizumab has been among the more contentious issues in breast cancer oncology of late. At the San Antonio Breast Cancer Symposium, investigators will add results from two more trials – the BEATRICE and LEA studies – to the ongoing debate.

BEATRICE Targets Early Triple-Negative Disease

Patients had to have confirmed triple-negative disease to be enrolled in the multinational, randomized, open-label BEATRICE study sponsored by Hoffman-La Roche, which markets bevacizumab (Avastin) in Europe.

Their tumors had to be operable primary invasive breast cancer, for which the patients completed definitive locoregional surgery. Those with locally advanced breast cancer were excluded from BEATRICE, which had a target enrollment of more than 2,500 patients.

The underlying question is whether adding 1 year of bevacizumab to standard adjuvant therapy is safe and can improve efficacy. Invasive disease–free survival is the primary outcome measure of BEATRICE, which began recruitment in 2007. "Primary" results are slated for presentation in General Session 6 at the San Antonio meeting (S6-5). Investigators also have prepared a biomarker analysis (Poster session 3, P3-06-34).

LEA Focuses on Advanced Hormone Receptor–Positive Disease

The first efficacy results from the phase III LEA study will focus on the addition of bevacizumab to first-line endocrine treatment in women who are eligible for hormonal therapy and also HER2 negative.

The Spanish Breast Cancer Research Group sponsored the trial in collaboration with the German Breast Group and Hoffmann-La Roche. It was designed to test the hypothesis that targeting the vascular endothelial growth factor (VEGF) with bevacizumab could present resistance to endocrine therapy "in patients with advanced breast cancer sensitive to such treatment" (Cancer Res. 2011;71(24 Supplement):OT3-01-15 [doi: 10.1158/0008-5472.SABCS11-OT3-01-15]).

The protocol called for enrollment of 378 patients with locally advanced or metastatic breast cancer. All received endocrine therapy with letrozole (Femara) or fulvestrant (Faslodex) during the trial; the experimental arm also received bevacizumab, and patients could continue on bevacizumab if they had not progressed on study.

Two-year progression-free survival is the primary end point of the trial, which began recruitment in November 2007. The first efficacy results will be presented in San Antonio (General session 1, S1-7).

Ongoing Quest to Define Who Would Benefit

Just over a year ago, on Nov. 18, 2011, Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced her decision to revoke an indication for bevacizumab in combination with paclitaxel for metastatic breast cancer. She acted after an emotional public hearing at which women with stage IV disease testified that they benefited from bevacizumab.

Earlier, the Oncologic Drugs Advisory Committee (ODAC) had voted unanimously in favor of withdrawal, citing toxicity and noting that confirmatory trials had not repeated the magnitude of benefit in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) on which accelerated approval had been based.

The National Comprehensive Cancer Network (NCCN) has stood by its endorsement of bevacizumab in combination with paclitaxel, however. "The data observed in the [E2100 trial] really had not changed from its approval previously, and we thought that if the data were compelling 2 years ago, why isn’t it compelling enough today?" explained Dr. Robert W. Carlson of Stanford (Calif.) University, chair of the NCCN’s breast cancer panel, after the FDA moved to revoke the indication.

Genentech, the U.S. drugmaker owned by Roche, expressed disappointment with the final FDA decision, and vowed to continue seeking biomarkers that would identify which breast cancer patients can benefit from bevacizumab.

This fall, investigators presented results of the Roche-sponsored TURANDOT trial at the annual meeting of the European Society for Medical Oncology in Vienna. They reported that paclitaxel appeared to be a better partner than capecitabine (Xeloda) for bevacizumab in patients with metastatic breast cancer, but overall survival was not significantly different between the two combinations, and results echoed outcomes in earlier trials.

Quality-of-life results from the TURANDOT trial will be presented in a poster session in San Antonio (Poster session, P5-17-03). Among the other scheduled bevacizumab presentations are:

• Final results of the single-arm, phase II AVANTHER trial from Spain. Investigators combined bevacizumab and trastuzumab (Herceptin) with weekly paclitaxel as a neoadjuvant treatment in HER2-positive breast cancer. Treatment was followed by surgery and adjuvant therapy (Poster session 1, P1-14-10).

• First toxicity results from the Eastern Cooperative Oncology Group E5103 trial. This randomized phase III study compared doxorubicin, cyclophosphamide, and paclitaxel with and without bevacizumab in patients with lymph node–positive or high-risk, lymph node–negative breast cancer (Poster session 5, P5-17-01).

The 2011 San Antonio Breast Cancer Symposium featured several clinical trials that would alter standard treatment of patients with advanced HER2-positive and hormone receptorpositive breast cancers.

A year later the key players are heading back to Texas with new, more refined analyses of pivotal data that have led so far to:

– Dual HER2 blockade, as validated by the pairing of pertuzumab (Perjeta) and trastuzumab (Herceptin) in the CLEOPATRA trial.

– The pairing of mTOR and aromatase inhibition, as validated by the combination of everolimus (Afinitor) and exemestane (Aromasin) in the BOLERO-2 trial.

"I think people are starting to use these treatments because they really remarkably influenced and extended progression-free survival and overall survival in these patients that have a relatively poor prognosis in metastatic breast cancer," Dr. C. Kent Osborne, codirector of the San Antonio Breast Cancer Symposium (SABCS), observed in an interview.

In addition, several trial reports will expand on the use of fulvestrant (Faslodex) in hormone receptorpositive breast cancer. Another prominent study presented in 2011 added fulvestrant to anastrozole (Arimidex), improving survival outcomes as well.

This, too, is having an impact on clinical practice, but less widely, said Dr. Osborne, professor of medicine and molecular and cellular biology and director of the Lester and Sue Smith Breast Center and of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

"There is another trial [FACT] of the same two drugs that did not show these same results, so there is a little bit of a discrepancy between the two trials, and maybe not everybody has adopted that approach," he said.

CLEOPATRA

The Food and Drug Administration gave approval on June 8, 2012, to pertuzumab, a new anti-HER2 therapy.* Approval was based on the phase III CLEOPATRA trial, which randomized 808 patients with metastatic or unresectable locally advanced HER2-positive cancer to a standard regimen of the original anti-HER2 therapy trastuzumab and the taxane docetaxel (Taxotere) plus placebo or both active drugs plus pertuzumab.

At SABCS 2011, Dr. José Baselga of Massachusetts General Hospital, Boston, reported that adding pertuzumab drove median progression-free survival from 12.4 months in the control group to 18.5 months a statistically significant difference that corresponds to a 38% reduction in the risk for progression or death. These results were published in the New England Journal of Medicine (2012;366:109-19).

This year, Dr. Baselga, recently named physician-in-chief of Memorial Hospital at Memorial Sloan-Kettering Cancer Center, New York, will be back (General session 5, S-1) with a biomarker analysis of the CLEOPATRA trial. CLEOPATRA investigators will also report on outcomes in elderly patients in the pertuzumab-trastuzumab-docetaxel cohort (Poster session 5, P5-18-01) and a confirmatory overall survival analysis (Poster session 5, P5-18-26).

A bonus: In the ongoing trials section, investigators will introduce PERUSE, a new Hoffman-La Roche–sponsored single-arm phase IIIb study of pertuzumab and trastuzumab plus a taxane as first-line therapy for patients with HER2-positive advanced breast cancer (Poster session OT-1, OT1-1-02).

BOLERO-2

Another FDA approval following SABCS 2011 expanded the indication on July 20, 2012, of everolimus to endorse its use in combination with exemestane in postmenopausal women whose hormone receptorpositive breast cancer recurred or progressed after treatment with letrozole (Femara) or anastrozole.

Everolimus targets the mammalian Target of Rapamycin (mTOR), while exemestane, letrozole, and anastrozole are aromatase inhibitors (AIs). The approval was based on findings of the phase III BOLERO-2 trial, which showed that simultaneous inhibition of the estrogen-signalling pathway with an AI and the PI3-kinase/AKT/mTOR pathway with an mTOR inhibitor could be effective in treatment-resistant, hormonal receptorpositive breast cancer.

At SABCS 2011 Dr. Gabriel Hortobagyi, professor and chair of breast medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, reported that adding everolimus to exemestane increased median progression-free interval from 3.2 months to 7.4 months and doubled the clinical benefit rate from 25.5% to 50.5%. Dr. Baselga was lead author of the published results (N. Engl. J. Med. 2012;366:520-29 [doi: 10.1056/NEJMoa1109653]).

This year, the BOLERO-2 investigators return to San Antonio with a poster giving the final progression-free survival analysis (Poster session 6, P6-04-02). Dr. Martine Piccart, professor of oncology at Université Libre de Bruxelles, director of the medicine department at Institut Jules Bordet (also in Brussels), and current president of the European Society for Medical Oncology, is listed as lead author.

Anastrazole and Fulvestrant

Also at SABCS 2011, Dr. Rita S. Mehta of the University of California, Irvine, reported that adding fulvestrant to anastrozole produced positive results as a first-line option for postmenopausal women with hormone receptor–positive breast cancer in the Southwest Oncology Group (SWOG)-S0226 trial.

Addition of fulvestrant prolonged progression-free survival by 1.5 months and overall survival by 6 months compared with monotherapy in the trial, for which results have since been published (N. Engl. J. Med. 2012;367:435-44 [doi:10.1056/NEJMoa1201622]).

Interestingly, the dose of fulvestrant (500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter) was below the current standard. In 2010, the FDA approved a dose of 500 mg per month based on a different study: the CONFIRM trial, for which investigators are to present a final overall survival analysis in the first general session at SABCS 2012 (General session 1, S1-4).

Also of note, investigators from France will present the first results of the randomized phase II Unicancer CARMINA 02 trial, which compares fulvestrant and anastrozole in the neoadjuvant setting among postmenopausal women with operable stage II or III breast cancer that is estrogen receptorpositive (Poster discussion session 7, PD07-04).

* This story was updated on 11/30/2012.

The 2011 San Antonio Breast Cancer Symposium featured several clinical trials that would alter standard treatment of patients with advanced HER2-positive and hormone receptorpositive breast cancers.

A year later the key players are heading back to Texas with new, more refined analyses of pivotal data that have led so far to:

– Dual HER2 blockade, as validated by the pairing of pertuzumab (Perjeta) and trastuzumab (Herceptin) in the CLEOPATRA trial.

– The pairing of mTOR and aromatase inhibition, as validated by the combination of everolimus (Afinitor) and exemestane (Aromasin) in the BOLERO-2 trial.

"I think people are starting to use these treatments because they really remarkably influenced and extended progression-free survival and overall survival in these patients that have a relatively poor prognosis in metastatic breast cancer," Dr. C. Kent Osborne, codirector of the San Antonio Breast Cancer Symposium (SABCS), observed in an interview.

In addition, several trial reports will expand on the use of fulvestrant (Faslodex) in hormone receptorpositive breast cancer. Another prominent study presented in 2011 added fulvestrant to anastrozole (Arimidex), improving survival outcomes as well.

This, too, is having an impact on clinical practice, but less widely, said Dr. Osborne, professor of medicine and molecular and cellular biology and director of the Lester and Sue Smith Breast Center and of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

"There is another trial [FACT] of the same two drugs that did not show these same results, so there is a little bit of a discrepancy between the two trials, and maybe not everybody has adopted that approach," he said.

CLEOPATRA

The Food and Drug Administration gave approval on June 8, 2012, to pertuzumab, a new anti-HER2 therapy.* Approval was based on the phase III CLEOPATRA trial, which randomized 808 patients with metastatic or unresectable locally advanced HER2-positive cancer to a standard regimen of the original anti-HER2 therapy trastuzumab and the taxane docetaxel (Taxotere) plus placebo or both active drugs plus pertuzumab.

At SABCS 2011, Dr. José Baselga of Massachusetts General Hospital, Boston, reported that adding pertuzumab drove median progression-free survival from 12.4 months in the control group to 18.5 months a statistically significant difference that corresponds to a 38% reduction in the risk for progression or death. These results were published in the New England Journal of Medicine (2012;366:109-19).

This year, Dr. Baselga, recently named physician-in-chief of Memorial Hospital at Memorial Sloan-Kettering Cancer Center, New York, will be back (General session 5, S-1) with a biomarker analysis of the CLEOPATRA trial. CLEOPATRA investigators will also report on outcomes in elderly patients in the pertuzumab-trastuzumab-docetaxel cohort (Poster session 5, P5-18-01) and a confirmatory overall survival analysis (Poster session 5, P5-18-26).

A bonus: In the ongoing trials section, investigators will introduce PERUSE, a new Hoffman-La Roche–sponsored single-arm phase IIIb study of pertuzumab and trastuzumab plus a taxane as first-line therapy for patients with HER2-positive advanced breast cancer (Poster session OT-1, OT1-1-02).

BOLERO-2

Another FDA approval following SABCS 2011 expanded the indication on July 20, 2012, of everolimus to endorse its use in combination with exemestane in postmenopausal women whose hormone receptorpositive breast cancer recurred or progressed after treatment with letrozole (Femara) or anastrozole.

Everolimus targets the mammalian Target of Rapamycin (mTOR), while exemestane, letrozole, and anastrozole are aromatase inhibitors (AIs). The approval was based on findings of the phase III BOLERO-2 trial, which showed that simultaneous inhibition of the estrogen-signalling pathway with an AI and the PI3-kinase/AKT/mTOR pathway with an mTOR inhibitor could be effective in treatment-resistant, hormonal receptorpositive breast cancer.

At SABCS 2011 Dr. Gabriel Hortobagyi, professor and chair of breast medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, reported that adding everolimus to exemestane increased median progression-free interval from 3.2 months to 7.4 months and doubled the clinical benefit rate from 25.5% to 50.5%. Dr. Baselga was lead author of the published results (N. Engl. J. Med. 2012;366:520-29 [doi: 10.1056/NEJMoa1109653]).

This year, the BOLERO-2 investigators return to San Antonio with a poster giving the final progression-free survival analysis (Poster session 6, P6-04-02). Dr. Martine Piccart, professor of oncology at Université Libre de Bruxelles, director of the medicine department at Institut Jules Bordet (also in Brussels), and current president of the European Society for Medical Oncology, is listed as lead author.

Anastrazole and Fulvestrant

Also at SABCS 2011, Dr. Rita S. Mehta of the University of California, Irvine, reported that adding fulvestrant to anastrozole produced positive results as a first-line option for postmenopausal women with hormone receptor–positive breast cancer in the Southwest Oncology Group (SWOG)-S0226 trial.

Addition of fulvestrant prolonged progression-free survival by 1.5 months and overall survival by 6 months compared with monotherapy in the trial, for which results have since been published (N. Engl. J. Med. 2012;367:435-44 [doi:10.1056/NEJMoa1201622]).

Interestingly, the dose of fulvestrant (500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter) was below the current standard. In 2010, the FDA approved a dose of 500 mg per month based on a different study: the CONFIRM trial, for which investigators are to present a final overall survival analysis in the first general session at SABCS 2012 (General session 1, S1-4).

Also of note, investigators from France will present the first results of the randomized phase II Unicancer CARMINA 02 trial, which compares fulvestrant and anastrozole in the neoadjuvant setting among postmenopausal women with operable stage II or III breast cancer that is estrogen receptorpositive (Poster discussion session 7, PD07-04).

* This story was updated on 11/30/2012.

The 2011 San Antonio Breast Cancer Symposium featured several clinical trials that would alter standard treatment of patients with advanced HER2-positive and hormone receptorpositive breast cancers.

A year later the key players are heading back to Texas with new, more refined analyses of pivotal data that have led so far to:

– Dual HER2 blockade, as validated by the pairing of pertuzumab (Perjeta) and trastuzumab (Herceptin) in the CLEOPATRA trial.

– The pairing of mTOR and aromatase inhibition, as validated by the combination of everolimus (Afinitor) and exemestane (Aromasin) in the BOLERO-2 trial.

"I think people are starting to use these treatments because they really remarkably influenced and extended progression-free survival and overall survival in these patients that have a relatively poor prognosis in metastatic breast cancer," Dr. C. Kent Osborne, codirector of the San Antonio Breast Cancer Symposium (SABCS), observed in an interview.

In addition, several trial reports will expand on the use of fulvestrant (Faslodex) in hormone receptorpositive breast cancer. Another prominent study presented in 2011 added fulvestrant to anastrozole (Arimidex), improving survival outcomes as well.

This, too, is having an impact on clinical practice, but less widely, said Dr. Osborne, professor of medicine and molecular and cellular biology and director of the Lester and Sue Smith Breast Center and of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston.

"There is another trial [FACT] of the same two drugs that did not show these same results, so there is a little bit of a discrepancy between the two trials, and maybe not everybody has adopted that approach," he said.

CLEOPATRA

The Food and Drug Administration gave approval on June 8, 2012, to pertuzumab, a new anti-HER2 therapy.* Approval was based on the phase III CLEOPATRA trial, which randomized 808 patients with metastatic or unresectable locally advanced HER2-positive cancer to a standard regimen of the original anti-HER2 therapy trastuzumab and the taxane docetaxel (Taxotere) plus placebo or both active drugs plus pertuzumab.

At SABCS 2011, Dr. José Baselga of Massachusetts General Hospital, Boston, reported that adding pertuzumab drove median progression-free survival from 12.4 months in the control group to 18.5 months a statistically significant difference that corresponds to a 38% reduction in the risk for progression or death. These results were published in the New England Journal of Medicine (2012;366:109-19).

This year, Dr. Baselga, recently named physician-in-chief of Memorial Hospital at Memorial Sloan-Kettering Cancer Center, New York, will be back (General session 5, S-1) with a biomarker analysis of the CLEOPATRA trial. CLEOPATRA investigators will also report on outcomes in elderly patients in the pertuzumab-trastuzumab-docetaxel cohort (Poster session 5, P5-18-01) and a confirmatory overall survival analysis (Poster session 5, P5-18-26).

A bonus: In the ongoing trials section, investigators will introduce PERUSE, a new Hoffman-La Roche–sponsored single-arm phase IIIb study of pertuzumab and trastuzumab plus a taxane as first-line therapy for patients with HER2-positive advanced breast cancer (Poster session OT-1, OT1-1-02).

BOLERO-2

Another FDA approval following SABCS 2011 expanded the indication on July 20, 2012, of everolimus to endorse its use in combination with exemestane in postmenopausal women whose hormone receptorpositive breast cancer recurred or progressed after treatment with letrozole (Femara) or anastrozole.

Everolimus targets the mammalian Target of Rapamycin (mTOR), while exemestane, letrozole, and anastrozole are aromatase inhibitors (AIs). The approval was based on findings of the phase III BOLERO-2 trial, which showed that simultaneous inhibition of the estrogen-signalling pathway with an AI and the PI3-kinase/AKT/mTOR pathway with an mTOR inhibitor could be effective in treatment-resistant, hormonal receptorpositive breast cancer.

At SABCS 2011 Dr. Gabriel Hortobagyi, professor and chair of breast medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, reported that adding everolimus to exemestane increased median progression-free interval from 3.2 months to 7.4 months and doubled the clinical benefit rate from 25.5% to 50.5%. Dr. Baselga was lead author of the published results (N. Engl. J. Med. 2012;366:520-29 [doi: 10.1056/NEJMoa1109653]).

This year, the BOLERO-2 investigators return to San Antonio with a poster giving the final progression-free survival analysis (Poster session 6, P6-04-02). Dr. Martine Piccart, professor of oncology at Université Libre de Bruxelles, director of the medicine department at Institut Jules Bordet (also in Brussels), and current president of the European Society for Medical Oncology, is listed as lead author.

Anastrazole and Fulvestrant

Also at SABCS 2011, Dr. Rita S. Mehta of the University of California, Irvine, reported that adding fulvestrant to anastrozole produced positive results as a first-line option for postmenopausal women with hormone receptor–positive breast cancer in the Southwest Oncology Group (SWOG)-S0226 trial.

Addition of fulvestrant prolonged progression-free survival by 1.5 months and overall survival by 6 months compared with monotherapy in the trial, for which results have since been published (N. Engl. J. Med. 2012;367:435-44 [doi:10.1056/NEJMoa1201622]).

Interestingly, the dose of fulvestrant (500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter) was below the current standard. In 2010, the FDA approved a dose of 500 mg per month based on a different study: the CONFIRM trial, for which investigators are to present a final overall survival analysis in the first general session at SABCS 2012 (General session 1, S1-4).

Also of note, investigators from France will present the first results of the randomized phase II Unicancer CARMINA 02 trial, which compares fulvestrant and anastrozole in the neoadjuvant setting among postmenopausal women with operable stage II or III breast cancer that is estrogen receptorpositive (Poster discussion session 7, PD07-04).

* This story was updated on 11/30/2012.

Treatment with vemurafenib, a RAF inhibitor, triggered proliferation of leukemia cells in a patient receiving therapy for metastatic melanoma, according to a case report published Nov. 7 in the New England Journal of Medicine.

Increased use of RAF inhibitors such as vemurafenib (Zelboraf) and the still-experimental dabrafenib are likely to stimulate additional cases of leukemia and other cancers in patients with coincidental RAS mutations, warn Dr. Paul D. Chapman of Memorial Sloan-Kettering Cancer Center in New York, and his coauthors.

Patients being treated with RAF inhibitors should be closely monitored, the authors advise, and any rapid rise in white-cell count "should be investigated promptly and the drug withheld until the cause of the rise in white cells is clarified." For now, they recommend that adjuvant treatment with RAF inhibitors should only be offered in the context of a clinical trial (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1208958]).

The patient in the case report, a 76-year-old man with stage IV melanoma, experienced improved breathing but also developed "new, profound fatigue" after starting vemurafenib, according to the report. Clinicians determined that he had marked elevations in his white blood count, along with increases in monocytes and neutrophils.

Vemurafenib was stopped, after which white cell and monocyte counts decreased. As the patient responded to treatment, he is again taking vemurafenib, but with clinicians adjusting the dose based on changes in white-cell counts.

Investigation of the case led the authors to hypothesize that vemurafenib was hyperactivating the ERK pathway and stimulating growth of chronic myelomonocytic leukemia cells carrying a preexisting NRAS mutation. They were able to verify this in vitro, and also came up with another hypothesis – that MEK inhibitors might weaken ERK signaling and suppress the proliferation of leukemic cells indirectly caused by vemurafenib.

As of publication, however, the authors were unable obtain a MEK inhibitor to test this hypothesis in a patient, as none are approved by the Food and Drug Administration. MEK inhibitors are being studied in combination with RAF inhibitors and have been shown to improve progression-free survival (N. Engl. J. Med. 2012;367:1694-703 [doi: 10.1056/NEJMoa1210093]).

About half of metastatic melanomas carry BRAF mutations, and about half of patients with BRAF mutations have been found to respond to vemurafenib. This led the FDA to approve vemurafenib in 2011 for treatment of inoperable or metastatic melanoma carrying the BRAF^V600E mutation. One side effect of vemurafenib treatment has been an increase in cutaneous skin conditions in about a quarter of patients.

"This case report shows that paradoxical ERK activation by RAF inhibitors is not restricted to proliferations such as squamous cell carcinomas and keratoacanthomas. It is clear that paradoxical activation can be seen in other premalignant lesions in which there are RAS mutations or other genetic changes that result in upstream activation of this pathway," Dr. Chapman and his coauthors wrote.

Dr. Chapman disclosed financial relationships with Roche/Genentech and GlaxoSmithKline and a pending institutional patent title Methods of Using BRAF Inhibitors for Cancer Screening and Imaging.

Treatment with vemurafenib, a RAF inhibitor, triggered proliferation of leukemia cells in a patient receiving therapy for metastatic melanoma, according to a case report published Nov. 7 in the New England Journal of Medicine.

Increased use of RAF inhibitors such as vemurafenib (Zelboraf) and the still-experimental dabrafenib are likely to stimulate additional cases of leukemia and other cancers in patients with coincidental RAS mutations, warn Dr. Paul D. Chapman of Memorial Sloan-Kettering Cancer Center in New York, and his coauthors.

Patients being treated with RAF inhibitors should be closely monitored, the authors advise, and any rapid rise in white-cell count "should be investigated promptly and the drug withheld until the cause of the rise in white cells is clarified." For now, they recommend that adjuvant treatment with RAF inhibitors should only be offered in the context of a clinical trial (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1208958]).

The patient in the case report, a 76-year-old man with stage IV melanoma, experienced improved breathing but also developed "new, profound fatigue" after starting vemurafenib, according to the report. Clinicians determined that he had marked elevations in his white blood count, along with increases in monocytes and neutrophils.

Vemurafenib was stopped, after which white cell and monocyte counts decreased. As the patient responded to treatment, he is again taking vemurafenib, but with clinicians adjusting the dose based on changes in white-cell counts.

Investigation of the case led the authors to hypothesize that vemurafenib was hyperactivating the ERK pathway and stimulating growth of chronic myelomonocytic leukemia cells carrying a preexisting NRAS mutation. They were able to verify this in vitro, and also came up with another hypothesis – that MEK inhibitors might weaken ERK signaling and suppress the proliferation of leukemic cells indirectly caused by vemurafenib.

As of publication, however, the authors were unable obtain a MEK inhibitor to test this hypothesis in a patient, as none are approved by the Food and Drug Administration. MEK inhibitors are being studied in combination with RAF inhibitors and have been shown to improve progression-free survival (N. Engl. J. Med. 2012;367:1694-703 [doi: 10.1056/NEJMoa1210093]).

About half of metastatic melanomas carry BRAF mutations, and about half of patients with BRAF mutations have been found to respond to vemurafenib. This led the FDA to approve vemurafenib in 2011 for treatment of inoperable or metastatic melanoma carrying the BRAF^V600E mutation. One side effect of vemurafenib treatment has been an increase in cutaneous skin conditions in about a quarter of patients.

"This case report shows that paradoxical ERK activation by RAF inhibitors is not restricted to proliferations such as squamous cell carcinomas and keratoacanthomas. It is clear that paradoxical activation can be seen in other premalignant lesions in which there are RAS mutations or other genetic changes that result in upstream activation of this pathway," Dr. Chapman and his coauthors wrote.

Dr. Chapman disclosed financial relationships with Roche/Genentech and GlaxoSmithKline and a pending institutional patent title Methods of Using BRAF Inhibitors for Cancer Screening and Imaging.

Treatment with vemurafenib, a RAF inhibitor, triggered proliferation of leukemia cells in a patient receiving therapy for metastatic melanoma, according to a case report published Nov. 7 in the New England Journal of Medicine.

Increased use of RAF inhibitors such as vemurafenib (Zelboraf) and the still-experimental dabrafenib are likely to stimulate additional cases of leukemia and other cancers in patients with coincidental RAS mutations, warn Dr. Paul D. Chapman of Memorial Sloan-Kettering Cancer Center in New York, and his coauthors.

Patients being treated with RAF inhibitors should be closely monitored, the authors advise, and any rapid rise in white-cell count "should be investigated promptly and the drug withheld until the cause of the rise in white cells is clarified." For now, they recommend that adjuvant treatment with RAF inhibitors should only be offered in the context of a clinical trial (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1208958]).

The patient in the case report, a 76-year-old man with stage IV melanoma, experienced improved breathing but also developed "new, profound fatigue" after starting vemurafenib, according to the report. Clinicians determined that he had marked elevations in his white blood count, along with increases in monocytes and neutrophils.

Vemurafenib was stopped, after which white cell and monocyte counts decreased. As the patient responded to treatment, he is again taking vemurafenib, but with clinicians adjusting the dose based on changes in white-cell counts.

Investigation of the case led the authors to hypothesize that vemurafenib was hyperactivating the ERK pathway and stimulating growth of chronic myelomonocytic leukemia cells carrying a preexisting NRAS mutation. They were able to verify this in vitro, and also came up with another hypothesis – that MEK inhibitors might weaken ERK signaling and suppress the proliferation of leukemic cells indirectly caused by vemurafenib.

As of publication, however, the authors were unable obtain a MEK inhibitor to test this hypothesis in a patient, as none are approved by the Food and Drug Administration. MEK inhibitors are being studied in combination with RAF inhibitors and have been shown to improve progression-free survival (N. Engl. J. Med. 2012;367:1694-703 [doi: 10.1056/NEJMoa1210093]).

About half of metastatic melanomas carry BRAF mutations, and about half of patients with BRAF mutations have been found to respond to vemurafenib. This led the FDA to approve vemurafenib in 2011 for treatment of inoperable or metastatic melanoma carrying the BRAF^V600E mutation. One side effect of vemurafenib treatment has been an increase in cutaneous skin conditions in about a quarter of patients.

"This case report shows that paradoxical ERK activation by RAF inhibitors is not restricted to proliferations such as squamous cell carcinomas and keratoacanthomas. It is clear that paradoxical activation can be seen in other premalignant lesions in which there are RAS mutations or other genetic changes that result in upstream activation of this pathway," Dr. Chapman and his coauthors wrote.

Dr. Chapman disclosed financial relationships with Roche/Genentech and GlaxoSmithKline and a pending institutional patent title Methods of Using BRAF Inhibitors for Cancer Screening and Imaging.

In bygone days, October presented itself in orange and black. Autumn leaves swirled in flame-colored piles. Pumpkins, pointy witches’ hats, and dark cats were everywhere, or so it seemed.

Now the hot fall color is pink. Pink ribbons are ubiquitous against nature’s orange-and-black backdrop. And pink wrist bands. And pink football cleats. And pink dresses on Michele Obama and Ann Romney at the second presidential debate. Even Halloween pumpkins are coming up pink all over.

@ Catherine Lane/istockphoto.co

October is National Breast Cancer Awareness month, and unless you have been to Mars during the last few weeks, it’s been hard to miss. Not only breast cancer charities, but also a slew of organizations has slapped pink ribbons on products to advance this popular cause.

For at least a decade, a smattering of groups and individuals has questioned who really profits. Since 2002, Think Before You Pink, a project of Breast Cancer Action, has been urging people to be skeptical before they buy into breast cancer promotions. This year, skeptics are questioning just how much the National Football League takes home after giving the American Cancer Society 5% of its profits on the high-priced pink hats and t-shirts being sold from the Breast Cancer Awareness page at the NFL online store.

Now New York Attorney General Eric T. Schneiderman has entered the fray with a best practices model for pink ribbon–style blends of commerce and charity. The best practices are designed "to promote transparency in charitable ‘cause marketing’ campaigns, a growing billion-dollar-a-year industry in which companies advertise that the sale or use of a product will result in a charitable contribution," according to a statement from Mr. Schneiderman.

His list follows a year-long review of pink ribbon and similar campaigns waged by nearly 150 companies. "While these campaigns have resulted in substantial donations, the attorney general’s review found that consumers often do not have sufficient information to understand how their purchases will benefit charity," the statement said.

The complete best practices and other guidance can be found here. Here, in short, is what the A.G. wants companies to do before they raise money in the name of breast cancer or any other cause:

• Clearly describe the promotion. Promotions should tell the name of the charity; the specific dollar amount per purchase that will go to charity; any caps on the donation; whether any consumer action is required to trigger a donation; and the start and end dates of the campaign.

• Make it easy to determine the donation amount. Companies should set a fixed dollar amount, such as 50 cents for every purchase, rather than use generic phrases like "a portion of proceeds" will go to charity.

• ‘Be transparent about what is not apparent.’ Conditions that are not obvious to consumers should be disclosed. Does the campaign have a contractual limit on the campaign? Will charitable contributions not be made in cash? Has a fixed amount been promised to the charity regardless of the number of products sold?

• Be transparent in social media. Sometimes a company promises to contribute to a cause for a "like" on Facebook or a "follow" on Twitter. The company should disclose how much it will donate for the action, the name of the recipient charity, when the campaign starts and ends, and whether there is a minimum or maximum amount it will donate. And it should be easy to see how much has been donated to date.

• Disclose how much money was raised. When the campaign is over, the company should say so – and tell everyone how much it gave to charity.

Finally, if all that is not clear enough, Mr. Schneiderman proposes a "Donation Information" label – similar to a nutrition label – that could be slapped on any product or website running a campaign.

So far, the Susan G. Komen for the Cure and Breast Cancer Research Foundation have signed on, the A.G. said. Who else is ready to show their true colors?

In bygone days, October presented itself in orange and black. Autumn leaves swirled in flame-colored piles. Pumpkins, pointy witches’ hats, and dark cats were everywhere, or so it seemed.

Now the hot fall color is pink. Pink ribbons are ubiquitous against nature’s orange-and-black backdrop. And pink wrist bands. And pink football cleats. And pink dresses on Michele Obama and Ann Romney at the second presidential debate. Even Halloween pumpkins are coming up pink all over.

@ Catherine Lane/istockphoto.co

October is National Breast Cancer Awareness month, and unless you have been to Mars during the last few weeks, it’s been hard to miss. Not only breast cancer charities, but also a slew of organizations has slapped pink ribbons on products to advance this popular cause.

For at least a decade, a smattering of groups and individuals has questioned who really profits. Since 2002, Think Before You Pink, a project of Breast Cancer Action, has been urging people to be skeptical before they buy into breast cancer promotions. This year, skeptics are questioning just how much the National Football League takes home after giving the American Cancer Society 5% of its profits on the high-priced pink hats and t-shirts being sold from the Breast Cancer Awareness page at the NFL online store.

Now New York Attorney General Eric T. Schneiderman has entered the fray with a best practices model for pink ribbon–style blends of commerce and charity. The best practices are designed "to promote transparency in charitable ‘cause marketing’ campaigns, a growing billion-dollar-a-year industry in which companies advertise that the sale or use of a product will result in a charitable contribution," according to a statement from Mr. Schneiderman.

His list follows a year-long review of pink ribbon and similar campaigns waged by nearly 150 companies. "While these campaigns have resulted in substantial donations, the attorney general’s review found that consumers often do not have sufficient information to understand how their purchases will benefit charity," the statement said.

The complete best practices and other guidance can be found here. Here, in short, is what the A.G. wants companies to do before they raise money in the name of breast cancer or any other cause:

• Clearly describe the promotion. Promotions should tell the name of the charity; the specific dollar amount per purchase that will go to charity; any caps on the donation; whether any consumer action is required to trigger a donation; and the start and end dates of the campaign.

• Make it easy to determine the donation amount. Companies should set a fixed dollar amount, such as 50 cents for every purchase, rather than use generic phrases like "a portion of proceeds" will go to charity.

• ‘Be transparent about what is not apparent.’ Conditions that are not obvious to consumers should be disclosed. Does the campaign have a contractual limit on the campaign? Will charitable contributions not be made in cash? Has a fixed amount been promised to the charity regardless of the number of products sold?

• Be transparent in social media. Sometimes a company promises to contribute to a cause for a "like" on Facebook or a "follow" on Twitter. The company should disclose how much it will donate for the action, the name of the recipient charity, when the campaign starts and ends, and whether there is a minimum or maximum amount it will donate. And it should be easy to see how much has been donated to date.

• Disclose how much money was raised. When the campaign is over, the company should say so – and tell everyone how much it gave to charity.

Finally, if all that is not clear enough, Mr. Schneiderman proposes a "Donation Information" label – similar to a nutrition label – that could be slapped on any product or website running a campaign.

So far, the Susan G. Komen for the Cure and Breast Cancer Research Foundation have signed on, the A.G. said. Who else is ready to show their true colors?

In bygone days, October presented itself in orange and black. Autumn leaves swirled in flame-colored piles. Pumpkins, pointy witches’ hats, and dark cats were everywhere, or so it seemed.

Now the hot fall color is pink. Pink ribbons are ubiquitous against nature’s orange-and-black backdrop. And pink wrist bands. And pink football cleats. And pink dresses on Michele Obama and Ann Romney at the second presidential debate. Even Halloween pumpkins are coming up pink all over.

@ Catherine Lane/istockphoto.co

October is National Breast Cancer Awareness month, and unless you have been to Mars during the last few weeks, it’s been hard to miss. Not only breast cancer charities, but also a slew of organizations has slapped pink ribbons on products to advance this popular cause.

For at least a decade, a smattering of groups and individuals has questioned who really profits. Since 2002, Think Before You Pink, a project of Breast Cancer Action, has been urging people to be skeptical before they buy into breast cancer promotions. This year, skeptics are questioning just how much the National Football League takes home after giving the American Cancer Society 5% of its profits on the high-priced pink hats and t-shirts being sold from the Breast Cancer Awareness page at the NFL online store.

Now New York Attorney General Eric T. Schneiderman has entered the fray with a best practices model for pink ribbon–style blends of commerce and charity. The best practices are designed "to promote transparency in charitable ‘cause marketing’ campaigns, a growing billion-dollar-a-year industry in which companies advertise that the sale or use of a product will result in a charitable contribution," according to a statement from Mr. Schneiderman.

His list follows a year-long review of pink ribbon and similar campaigns waged by nearly 150 companies. "While these campaigns have resulted in substantial donations, the attorney general’s review found that consumers often do not have sufficient information to understand how their purchases will benefit charity," the statement said.

The complete best practices and other guidance can be found here. Here, in short, is what the A.G. wants companies to do before they raise money in the name of breast cancer or any other cause:

• Clearly describe the promotion. Promotions should tell the name of the charity; the specific dollar amount per purchase that will go to charity; any caps on the donation; whether any consumer action is required to trigger a donation; and the start and end dates of the campaign.

• Make it easy to determine the donation amount. Companies should set a fixed dollar amount, such as 50 cents for every purchase, rather than use generic phrases like "a portion of proceeds" will go to charity.

• ‘Be transparent about what is not apparent.’ Conditions that are not obvious to consumers should be disclosed. Does the campaign have a contractual limit on the campaign? Will charitable contributions not be made in cash? Has a fixed amount been promised to the charity regardless of the number of products sold?

• Be transparent in social media. Sometimes a company promises to contribute to a cause for a "like" on Facebook or a "follow" on Twitter. The company should disclose how much it will donate for the action, the name of the recipient charity, when the campaign starts and ends, and whether there is a minimum or maximum amount it will donate. And it should be easy to see how much has been donated to date.

• Disclose how much money was raised. When the campaign is over, the company should say so – and tell everyone how much it gave to charity.

Finally, if all that is not clear enough, Mr. Schneiderman proposes a "Donation Information" label – similar to a nutrition label – that could be slapped on any product or website running a campaign.

So far, the Susan G. Komen for the Cure and Breast Cancer Research Foundation have signed on, the A.G. said. Who else is ready to show their true colors?

The first ultrasound device to boost breast cancer detection in women with dense breasts won approval Sept. 18 from the Food and Drug Administration as a screening tool for use in combination with standard mammography.

The somo-v Automated Breast Ultrasound System (ABUS) device was approved in 2005 as an adjunct to mammography. This new decision broadens its authorized use to asymptomatic women who have no evidence of breast cancer and whose mammograms are negative.

Images: ©2011 U-Systems, Inc. All Rights Reserved.

Whether a woman has dense breasts would be determined by a physician, according to the FDA announcement. Women who have had a previous clinical breast intervention, such as a surgery or biopsy, would not be eligible for the device, "since this might alter the appearance of breast tissue in an ultrasound image," the FDA said.

Breast cancer detection by mammography is more challenging in dense breasts, which have a high amount of fibroglandular tissue, as compared with the fatty tissue seen in less-dense breasts. "Fibroglandular breast tissue and tumors both appear as solid white areas on mammograms. As a result, dense breast tissue may obscure smaller tumors, potentially delaying detection of breast cancer," the FDA noted in its announcement.

A recent study reported dense breasts do not increase risk of death from breast cancer, but that dense breasts are associated with greater risk of developing the disease (J. Natl. Cancer Inst. 2012 [doi:10.1093/jnci/djs327]).

In addition, lobbying efforts have sought to mandate that mammography reports notify women who have dense breasts that they may benefit from additional screening.

The go-ahead for ultrasound screening follows a unanimous 13-0 endorsement in April from the agency’s Radiological Devices Panel. That advisory group agreed that the device’s benefits outweigh any risks for breast cancer screening. The FDA had been concerned about the generalization of a pivotal study to a broad population but the panel deemed the noninvasive device to be safe and effective.

The retrospective multireader study involved 200 women at 13 U.S. sites. All had dense breasts, and reviews by board-certified radiologists showed a statistically significant increase in breast cancer detection when the device was used with mammography as compared with mammography alone.

As a condition of approval, Sunnyvale, Calif.–based U-Systems Inc., which makes the device, must provide thorough training for physicians and technologists, and provide facilities with "a manual clearly defining system tests required for initial, periodic, and yearly quality control measures."

"Enabling radiologists to use the information obtained from mammography and integrate that with the information obtained with ultrasound, leverages the potential of ABUS in a screening environment to find the 30% additional cancers that would not have been found with mammography alone," said Ron Ho, president and CEO of U-Systems, maker of the somo-v ABUS. "Research shows that ABUS can help find cancer in women with dense breasts, and that the cancers are smaller and early stage. With formal approval, we are moving rapidly from development to commercialization and look forward to making the somo-v ABUS system more widely available across the United States."

The first ultrasound device to boost breast cancer detection in women with dense breasts won approval Sept. 18 from the Food and Drug Administration as a screening tool for use in combination with standard mammography.

The somo-v Automated Breast Ultrasound System (ABUS) device was approved in 2005 as an adjunct to mammography. This new decision broadens its authorized use to asymptomatic women who have no evidence of breast cancer and whose mammograms are negative.

Images: ©2011 U-Systems, Inc. All Rights Reserved.

Whether a woman has dense breasts would be determined by a physician, according to the FDA announcement. Women who have had a previous clinical breast intervention, such as a surgery or biopsy, would not be eligible for the device, "since this might alter the appearance of breast tissue in an ultrasound image," the FDA said.

Breast cancer detection by mammography is more challenging in dense breasts, which have a high amount of fibroglandular tissue, as compared with the fatty tissue seen in less-dense breasts. "Fibroglandular breast tissue and tumors both appear as solid white areas on mammograms. As a result, dense breast tissue may obscure smaller tumors, potentially delaying detection of breast cancer," the FDA noted in its announcement.

A recent study reported dense breasts do not increase risk of death from breast cancer, but that dense breasts are associated with greater risk of developing the disease (J. Natl. Cancer Inst. 2012 [doi:10.1093/jnci/djs327]).

In addition, lobbying efforts have sought to mandate that mammography reports notify women who have dense breasts that they may benefit from additional screening.

The go-ahead for ultrasound screening follows a unanimous 13-0 endorsement in April from the agency’s Radiological Devices Panel. That advisory group agreed that the device’s benefits outweigh any risks for breast cancer screening. The FDA had been concerned about the generalization of a pivotal study to a broad population but the panel deemed the noninvasive device to be safe and effective.

The retrospective multireader study involved 200 women at 13 U.S. sites. All had dense breasts, and reviews by board-certified radiologists showed a statistically significant increase in breast cancer detection when the device was used with mammography as compared with mammography alone.

As a condition of approval, Sunnyvale, Calif.–based U-Systems Inc., which makes the device, must provide thorough training for physicians and technologists, and provide facilities with "a manual clearly defining system tests required for initial, periodic, and yearly quality control measures."

"Enabling radiologists to use the information obtained from mammography and integrate that with the information obtained with ultrasound, leverages the potential of ABUS in a screening environment to find the 30% additional cancers that would not have been found with mammography alone," said Ron Ho, president and CEO of U-Systems, maker of the somo-v ABUS. "Research shows that ABUS can help find cancer in women with dense breasts, and that the cancers are smaller and early stage. With formal approval, we are moving rapidly from development to commercialization and look forward to making the somo-v ABUS system more widely available across the United States."

The first ultrasound device to boost breast cancer detection in women with dense breasts won approval Sept. 18 from the Food and Drug Administration as a screening tool for use in combination with standard mammography.

The somo-v Automated Breast Ultrasound System (ABUS) device was approved in 2005 as an adjunct to mammography. This new decision broadens its authorized use to asymptomatic women who have no evidence of breast cancer and whose mammograms are negative.

Images: ©2011 U-Systems, Inc. All Rights Reserved.

Whether a woman has dense breasts would be determined by a physician, according to the FDA announcement. Women who have had a previous clinical breast intervention, such as a surgery or biopsy, would not be eligible for the device, "since this might alter the appearance of breast tissue in an ultrasound image," the FDA said.

Breast cancer detection by mammography is more challenging in dense breasts, which have a high amount of fibroglandular tissue, as compared with the fatty tissue seen in less-dense breasts. "Fibroglandular breast tissue and tumors both appear as solid white areas on mammograms. As a result, dense breast tissue may obscure smaller tumors, potentially delaying detection of breast cancer," the FDA noted in its announcement.

A recent study reported dense breasts do not increase risk of death from breast cancer, but that dense breasts are associated with greater risk of developing the disease (J. Natl. Cancer Inst. 2012 [doi:10.1093/jnci/djs327]).

In addition, lobbying efforts have sought to mandate that mammography reports notify women who have dense breasts that they may benefit from additional screening.

The go-ahead for ultrasound screening follows a unanimous 13-0 endorsement in April from the agency’s Radiological Devices Panel. That advisory group agreed that the device’s benefits outweigh any risks for breast cancer screening. The FDA had been concerned about the generalization of a pivotal study to a broad population but the panel deemed the noninvasive device to be safe and effective.

The retrospective multireader study involved 200 women at 13 U.S. sites. All had dense breasts, and reviews by board-certified radiologists showed a statistically significant increase in breast cancer detection when the device was used with mammography as compared with mammography alone.

As a condition of approval, Sunnyvale, Calif.–based U-Systems Inc., which makes the device, must provide thorough training for physicians and technologists, and provide facilities with "a manual clearly defining system tests required for initial, periodic, and yearly quality control measures."

"Enabling radiologists to use the information obtained from mammography and integrate that with the information obtained with ultrasound, leverages the potential of ABUS in a screening environment to find the 30% additional cancers that would not have been found with mammography alone," said Ron Ho, president and CEO of U-Systems, maker of the somo-v ABUS. "Research shows that ABUS can help find cancer in women with dense breasts, and that the cancers are smaller and early stage. With formal approval, we are moving rapidly from development to commercialization and look forward to making the somo-v ABUS system more widely available across the United States."

Enzalutamide – an oral agent formerly known as MDV3100 – has won Food and Drug Administration approval as a second-line treatment for metastatic castration-resistant prostate cancer.

The new agent, to be marketed under the brand name Xtandi, is the latest in a stream of new therapies transforming treatment of prostate cancer. Other approvals within the last 3 years include the cancer vaccine sipuleucel-T (Provenge), abiraterone (Zytiga), cabazitaxel (Jevtana), and denosumab (Prolia, Xgeva) for bone-related indications.

Only the timing of the enzalutamide decision, announced Aug. 31 at the start of the Labor Day weekend, was a surprise. It came 3 months earlier than the Nov. 22 deadline set for FDA action under the agency’s priority review program.

"The need for additional treatment options for advanced prostate cancer continues to be important for patients. Xtandi is the latest treatment for this disease to demonstrate its ability to extend a patient’s life," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Enzalutamide inhibits signaling by the androgen receptor. Approval is based on results of the randomized, double-blind, placebo-controlled AFFIRM trial, the results of which were published Aug. 15 online (N. Engl. J. Med. 2012 [doi: 10.1056/NEJMoa1207506]).

The new agent prolonged overall survival by a median of 4.8 months and reduced the risk of death by 37% in the study, which evaluated 1,199 patients with metastatic castration-resistant prostate cancer who had received prior treatment with docetaxel (Taxotere). Medium overall survival reached 18.4 months with enzalutamide vs. 13.6 months with placebo.

The FDA noted that about 1% of patients receiving enzalutamide had seizures and stopped therapy. The study had excluded patients with "a history of seizure, an underlying brain injury with loss of consciousness, a temporary decrease in blood to the brain within the past 12 months, a stroke, brain metastases, an abnormal connection of the arteries and veins in the brain, or patients taking medications that may lower the seizure threshold."

The announcement advised, "The safety of Xtandi is unknown in patients with these conditions."

Otherwise, the most common side effects listed by the FDA were "weakness or fatigue, back pain, diarrhea, joint pain, hot flush, tissue swelling, musculoskeletal pain, headache, upper respiratory infections, dizziness, spinal cord compression and cauda equina syndrome, muscular weakness, difficulty sleeping, lower respiratory infections, blood in urine, tingling sensation, anxiety, and high blood pressure."

Enzalutamide will be co-marketed by Astellas Pharma U.S., Inc. of Northbrook, Ill., and Medivation Inc. of San Francisco.

Enzalutamide – an oral agent formerly known as MDV3100 – has won Food and Drug Administration approval as a second-line treatment for metastatic castration-resistant prostate cancer.

The new agent, to be marketed under the brand name Xtandi, is the latest in a stream of new therapies transforming treatment of prostate cancer. Other approvals within the last 3 years include the cancer vaccine sipuleucel-T (Provenge), abiraterone (Zytiga), cabazitaxel (Jevtana), and denosumab (Prolia, Xgeva) for bone-related indications.

Only the timing of the enzalutamide decision, announced Aug. 31 at the start of the Labor Day weekend, was a surprise. It came 3 months earlier than the Nov. 22 deadline set for FDA action under the agency’s priority review program.

"The need for additional treatment options for advanced prostate cancer continues to be important for patients. Xtandi is the latest treatment for this disease to demonstrate its ability to extend a patient’s life," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Enzalutamide inhibits signaling by the androgen receptor. Approval is based on results of the randomized, double-blind, placebo-controlled AFFIRM trial, the results of which were published Aug. 15 online (N. Engl. J. Med. 2012 [doi: 10.1056/NEJMoa1207506]).

The new agent prolonged overall survival by a median of 4.8 months and reduced the risk of death by 37% in the study, which evaluated 1,199 patients with metastatic castration-resistant prostate cancer who had received prior treatment with docetaxel (Taxotere). Medium overall survival reached 18.4 months with enzalutamide vs. 13.6 months with placebo.

The FDA noted that about 1% of patients receiving enzalutamide had seizures and stopped therapy. The study had excluded patients with "a history of seizure, an underlying brain injury with loss of consciousness, a temporary decrease in blood to the brain within the past 12 months, a stroke, brain metastases, an abnormal connection of the arteries and veins in the brain, or patients taking medications that may lower the seizure threshold."

The announcement advised, "The safety of Xtandi is unknown in patients with these conditions."

Otherwise, the most common side effects listed by the FDA were "weakness or fatigue, back pain, diarrhea, joint pain, hot flush, tissue swelling, musculoskeletal pain, headache, upper respiratory infections, dizziness, spinal cord compression and cauda equina syndrome, muscular weakness, difficulty sleeping, lower respiratory infections, blood in urine, tingling sensation, anxiety, and high blood pressure."

Enzalutamide will be co-marketed by Astellas Pharma U.S., Inc. of Northbrook, Ill., and Medivation Inc. of San Francisco.

Enzalutamide – an oral agent formerly known as MDV3100 – has won Food and Drug Administration approval as a second-line treatment for metastatic castration-resistant prostate cancer.

The new agent, to be marketed under the brand name Xtandi, is the latest in a stream of new therapies transforming treatment of prostate cancer. Other approvals within the last 3 years include the cancer vaccine sipuleucel-T (Provenge), abiraterone (Zytiga), cabazitaxel (Jevtana), and denosumab (Prolia, Xgeva) for bone-related indications.

Only the timing of the enzalutamide decision, announced Aug. 31 at the start of the Labor Day weekend, was a surprise. It came 3 months earlier than the Nov. 22 deadline set for FDA action under the agency’s priority review program.

"The need for additional treatment options for advanced prostate cancer continues to be important for patients. Xtandi is the latest treatment for this disease to demonstrate its ability to extend a patient’s life," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Enzalutamide inhibits signaling by the androgen receptor. Approval is based on results of the randomized, double-blind, placebo-controlled AFFIRM trial, the results of which were published Aug. 15 online (N. Engl. J. Med. 2012 [doi: 10.1056/NEJMoa1207506]).

The new agent prolonged overall survival by a median of 4.8 months and reduced the risk of death by 37% in the study, which evaluated 1,199 patients with metastatic castration-resistant prostate cancer who had received prior treatment with docetaxel (Taxotere). Medium overall survival reached 18.4 months with enzalutamide vs. 13.6 months with placebo.

The FDA noted that about 1% of patients receiving enzalutamide had seizures and stopped therapy. The study had excluded patients with "a history of seizure, an underlying brain injury with loss of consciousness, a temporary decrease in blood to the brain within the past 12 months, a stroke, brain metastases, an abnormal connection of the arteries and veins in the brain, or patients taking medications that may lower the seizure threshold."

The announcement advised, "The safety of Xtandi is unknown in patients with these conditions."

Otherwise, the most common side effects listed by the FDA were "weakness or fatigue, back pain, diarrhea, joint pain, hot flush, tissue swelling, musculoskeletal pain, headache, upper respiratory infections, dizziness, spinal cord compression and cauda equina syndrome, muscular weakness, difficulty sleeping, lower respiratory infections, blood in urine, tingling sensation, anxiety, and high blood pressure."

Enzalutamide will be co-marketed by Astellas Pharma U.S., Inc. of Northbrook, Ill., and Medivation Inc. of San Francisco.

A new quality of life analysis adds fuel for both sides in the ongoing debate over benefit versus harm of routine PSA screening for prostate cancer in asymptomatic men, according to a report in the New England Journal of Medicine.

Researchers applied complex modeling to the European Randomized Study of Screening for Prostate Cancer (ERSPC), which reported screening cuts prostate cancer mortality by 29%. They agreed that screening saves lives but found that the benefit was undercut by long-term effects of overdiagnosis and overtreatment.

The new analysis calculates the ERSPC results in quality-adjusted life-years (QALYs), a measure the investigators based on health states ranging from "death or worst imaginable health" to full health and on treatment-related complications such as urinary incontinence, bowel dysfunction, and sexual dysfunction.

"Our model predicts that there would be nine fewer prostate cancer deaths and 73 life-years gained over the lifetime of 1,000 men who underwent annual screening between the ages of 55 and 69 years," write Dr. Eveline A.M. Heijnsdijk of Erasmus Medical Center, Rotterdam, the Netherlands, and her coauthors.

"The harms caused by the introduction of such screening would be the overdiagnosis and overtreatment of 45 cases and the loss of 1,134 life-years free of prostate cancer (i.e., lead-time years). After adjustment of the number of life-years gained from screening by consideration of quality-of-life effects, 56 QALYs would be gained, which is a 23% reduction from the predicted number of life-years gained."

Extending screening to men aged 74 years would increase the number of unadjusted life-years gained to 82, but QALYs would stay the same at 56, according to the authors (N. Engl. J. Med. 2012;367:595-605 [doi: 10.1056/NEJMoa1201637]).

"The predicted adjustment for quality of life is due to the long-term side effects from treatment. Men in whom cancer has been overdiagnosed and those in whom cancer has not been overdiagnosed will live many years with the adverse effects of treatment," they write.

The U.S. Preventive Services Task Force (USPSTF) set off a furor in May when it took a stand against PSA screening for prostate cancer in healthy men, arguing that the harms outweigh the benefits. Debate has centered on interpretation of data from the ERSPC trial (N. Engl. J. Med. 2012;366:981-90) and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (N. Engl. J. Med. 2009;360:1310-9), with proponents of universal screening arguing that it saves lives.

Dr. Heijnsdijk and her coauthors did not take a stand on screening, proposing instead that more long-term data are needed along with more research and more modeling to calculate cost-effectiveness.

"It is essential to await longer follow-up data from the ERSPC, as well as longer-term data on how treatment and active surveillance affect long-term quality of life, before more general recommendations can be made regarding mass PSA screening," they conclude.

The analysis was supported by grants from the Netherlands Organization for Health Research and Development, Europe Against Cancer, the European Union; agencies or health authorities in participating countries; and by unconditional grants from Beckman Coulter.

Dr. Heijnsdijk disclosed receiving consulting fees from Beckman Coulter and her coauthors reported relationships with various companies. Dr. Sox is a former chair of the U.S. Preventive Services Task Force and serves on the board of the Informed Medical Decisions Foundation, which makes decision aids for prostate cancer screening.

A new quality of life analysis adds fuel for both sides in the ongoing debate over benefit versus harm of routine PSA screening for prostate cancer in asymptomatic men, according to a report in the New England Journal of Medicine.

Researchers applied complex modeling to the European Randomized Study of Screening for Prostate Cancer (ERSPC), which reported screening cuts prostate cancer mortality by 29%. They agreed that screening saves lives but found that the benefit was undercut by long-term effects of overdiagnosis and overtreatment.

The new analysis calculates the ERSPC results in quality-adjusted life-years (QALYs), a measure the investigators based on health states ranging from "death or worst imaginable health" to full health and on treatment-related complications such as urinary incontinence, bowel dysfunction, and sexual dysfunction.

"Our model predicts that there would be nine fewer prostate cancer deaths and 73 life-years gained over the lifetime of 1,000 men who underwent annual screening between the ages of 55 and 69 years," write Dr. Eveline A.M. Heijnsdijk of Erasmus Medical Center, Rotterdam, the Netherlands, and her coauthors.

"The harms caused by the introduction of such screening would be the overdiagnosis and overtreatment of 45 cases and the loss of 1,134 life-years free of prostate cancer (i.e., lead-time years). After adjustment of the number of life-years gained from screening by consideration of quality-of-life effects, 56 QALYs would be gained, which is a 23% reduction from the predicted number of life-years gained."

Extending screening to men aged 74 years would increase the number of unadjusted life-years gained to 82, but QALYs would stay the same at 56, according to the authors (N. Engl. J. Med. 2012;367:595-605 [doi: 10.1056/NEJMoa1201637]).

"The predicted adjustment for quality of life is due to the long-term side effects from treatment. Men in whom cancer has been overdiagnosed and those in whom cancer has not been overdiagnosed will live many years with the adverse effects of treatment," they write.

The U.S. Preventive Services Task Force (USPSTF) set off a furor in May when it took a stand against PSA screening for prostate cancer in healthy men, arguing that the harms outweigh the benefits. Debate has centered on interpretation of data from the ERSPC trial (N. Engl. J. Med. 2012;366:981-90) and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (N. Engl. J. Med. 2009;360:1310-9), with proponents of universal screening arguing that it saves lives.

Dr. Heijnsdijk and her coauthors did not take a stand on screening, proposing instead that more long-term data are needed along with more research and more modeling to calculate cost-effectiveness.

"It is essential to await longer follow-up data from the ERSPC, as well as longer-term data on how treatment and active surveillance affect long-term quality of life, before more general recommendations can be made regarding mass PSA screening," they conclude.

The analysis was supported by grants from the Netherlands Organization for Health Research and Development, Europe Against Cancer, the European Union; agencies or health authorities in participating countries; and by unconditional grants from Beckman Coulter.

Dr. Heijnsdijk disclosed receiving consulting fees from Beckman Coulter and her coauthors reported relationships with various companies. Dr. Sox is a former chair of the U.S. Preventive Services Task Force and serves on the board of the Informed Medical Decisions Foundation, which makes decision aids for prostate cancer screening.

A new quality of life analysis adds fuel for both sides in the ongoing debate over benefit versus harm of routine PSA screening for prostate cancer in asymptomatic men, according to a report in the New England Journal of Medicine.

Researchers applied complex modeling to the European Randomized Study of Screening for Prostate Cancer (ERSPC), which reported screening cuts prostate cancer mortality by 29%. They agreed that screening saves lives but found that the benefit was undercut by long-term effects of overdiagnosis and overtreatment.

The new analysis calculates the ERSPC results in quality-adjusted life-years (QALYs), a measure the investigators based on health states ranging from "death or worst imaginable health" to full health and on treatment-related complications such as urinary incontinence, bowel dysfunction, and sexual dysfunction.

"Our model predicts that there would be nine fewer prostate cancer deaths and 73 life-years gained over the lifetime of 1,000 men who underwent annual screening between the ages of 55 and 69 years," write Dr. Eveline A.M. Heijnsdijk of Erasmus Medical Center, Rotterdam, the Netherlands, and her coauthors.

"The harms caused by the introduction of such screening would be the overdiagnosis and overtreatment of 45 cases and the loss of 1,134 life-years free of prostate cancer (i.e., lead-time years). After adjustment of the number of life-years gained from screening by consideration of quality-of-life effects, 56 QALYs would be gained, which is a 23% reduction from the predicted number of life-years gained."

Extending screening to men aged 74 years would increase the number of unadjusted life-years gained to 82, but QALYs would stay the same at 56, according to the authors (N. Engl. J. Med. 2012;367:595-605 [doi: 10.1056/NEJMoa1201637]).

"The predicted adjustment for quality of life is due to the long-term side effects from treatment. Men in whom cancer has been overdiagnosed and those in whom cancer has not been overdiagnosed will live many years with the adverse effects of treatment," they write.

The U.S. Preventive Services Task Force (USPSTF) set off a furor in May when it took a stand against PSA screening for prostate cancer in healthy men, arguing that the harms outweigh the benefits. Debate has centered on interpretation of data from the ERSPC trial (N. Engl. J. Med. 2012;366:981-90) and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (N. Engl. J. Med. 2009;360:1310-9), with proponents of universal screening arguing that it saves lives.

Dr. Heijnsdijk and her coauthors did not take a stand on screening, proposing instead that more long-term data are needed along with more research and more modeling to calculate cost-effectiveness.

"It is essential to await longer follow-up data from the ERSPC, as well as longer-term data on how treatment and active surveillance affect long-term quality of life, before more general recommendations can be made regarding mass PSA screening," they conclude.

The analysis was supported by grants from the Netherlands Organization for Health Research and Development, Europe Against Cancer, the European Union; agencies or health authorities in participating countries; and by unconditional grants from Beckman Coulter.

Dr. Heijnsdijk disclosed receiving consulting fees from Beckman Coulter and her coauthors reported relationships with various companies. Dr. Sox is a former chair of the U.S. Preventive Services Task Force and serves on the board of the Informed Medical Decisions Foundation, which makes decision aids for prostate cancer screening.

A regimen combining anastrozole with fulvestrant added 6 months to the lives of postmenopausal women with previously untreated, hormone receptor–positive metastatic breast cancer, according to clinical trial results published August 2 in the New England Journal of Medicine.

Overall survival increased significantly from a median of 41.3 months with anastrozole (Arimidex) alone to 47.7 months with anastrozole and fulvestrant (Faslodex) in the Southwest Oncology Group (SWOG) S0226 trial. The combination’s survival advantage prevailed with a hazard ratio for death of 0.81 despite crossover to single-agent fulvestrant by 41% of patients in the control group after disease progression.

Median progression-free survival, the trial’s primary end point, also showed a statistically significant improvement from 13.5 months to 15 months, Dr. Rita S. Mehta of the University of California, Irvine, Medical Center, and her associates report (N. Engl. J. Med. 2012; 367: 435-4 [doi: 10.1056/NEJMoa1201622]).

The study randomized 707 patients, of whom 694 were included in the intention-to-treat analysis. All participants received 1 mg of anastrozole orally each day. Those assigned to the experimental arm also received a 500 mg loading dose of fulvestrant administered intramuscularly on day 1, followed by 250 mg on days 14 and 28 of 28-day cycles. The fulvestrant dose is lower than the 500-mg dose approved by the Food and Drug Administration, and the protocol was amended on Feb. 2, 2011 to allow patients in both study arms to receive the higher dose upon progression.*

Although three deaths may have been associated with the combination treatment, the investigators report that grade 3-5 adverse events were not significantly different between the two arms of the trial.

The study was funded by the National Cancer Institute and AstraZeneca. Disclosures for the individual authors are posted at www.nejm.com.

The NEJM report expands on results presented at the San Antonio Breast Cancer Symposium in December 2012. Dr. Hope Rugo and Dr. William Gradishar, associate editors of The Oncology Report, a publication of Elsevier, discussed the regimen at that meeting in the accompanying video.

*Correction, 8/1/2012: An earlier version of this story misstated the date of FDA approval for the 500-mg dose of fulvestrant.

A regimen combining anastrozole with fulvestrant added 6 months to the lives of postmenopausal women with previously untreated, hormone receptor–positive metastatic breast cancer, according to clinical trial results published August 2 in the New England Journal of Medicine.

Overall survival increased significantly from a median of 41.3 months with anastrozole (Arimidex) alone to 47.7 months with anastrozole and fulvestrant (Faslodex) in the Southwest Oncology Group (SWOG) S0226 trial. The combination’s survival advantage prevailed with a hazard ratio for death of 0.81 despite crossover to single-agent fulvestrant by 41% of patients in the control group after disease progression.

Median progression-free survival, the trial’s primary end point, also showed a statistically significant improvement from 13.5 months to 15 months, Dr. Rita S. Mehta of the University of California, Irvine, Medical Center, and her associates report (N. Engl. J. Med. 2012; 367: 435-4 [doi: 10.1056/NEJMoa1201622]).

The study randomized 707 patients, of whom 694 were included in the intention-to-treat analysis. All participants received 1 mg of anastrozole orally each day. Those assigned to the experimental arm also received a 500 mg loading dose of fulvestrant administered intramuscularly on day 1, followed by 250 mg on days 14 and 28 of 28-day cycles. The fulvestrant dose is lower than the 500-mg dose approved by the Food and Drug Administration, and the protocol was amended on Feb. 2, 2011 to allow patients in both study arms to receive the higher dose upon progression.*

Although three deaths may have been associated with the combination treatment, the investigators report that grade 3-5 adverse events were not significantly different between the two arms of the trial.

The study was funded by the National Cancer Institute and AstraZeneca. Disclosures for the individual authors are posted at www.nejm.com.

The NEJM report expands on results presented at the San Antonio Breast Cancer Symposium in December 2012. Dr. Hope Rugo and Dr. William Gradishar, associate editors of The Oncology Report, a publication of Elsevier, discussed the regimen at that meeting in the accompanying video.

*Correction, 8/1/2012: An earlier version of this story misstated the date of FDA approval for the 500-mg dose of fulvestrant.

A regimen combining anastrozole with fulvestrant added 6 months to the lives of postmenopausal women with previously untreated, hormone receptor–positive metastatic breast cancer, according to clinical trial results published August 2 in the New England Journal of Medicine.

Overall survival increased significantly from a median of 41.3 months with anastrozole (Arimidex) alone to 47.7 months with anastrozole and fulvestrant (Faslodex) in the Southwest Oncology Group (SWOG) S0226 trial. The combination’s survival advantage prevailed with a hazard ratio for death of 0.81 despite crossover to single-agent fulvestrant by 41% of patients in the control group after disease progression.

Median progression-free survival, the trial’s primary end point, also showed a statistically significant improvement from 13.5 months to 15 months, Dr. Rita S. Mehta of the University of California, Irvine, Medical Center, and her associates report (N. Engl. J. Med. 2012; 367: 435-4 [doi: 10.1056/NEJMoa1201622]).

The study randomized 707 patients, of whom 694 were included in the intention-to-treat analysis. All participants received 1 mg of anastrozole orally each day. Those assigned to the experimental arm also received a 500 mg loading dose of fulvestrant administered intramuscularly on day 1, followed by 250 mg on days 14 and 28 of 28-day cycles. The fulvestrant dose is lower than the 500-mg dose approved by the Food and Drug Administration, and the protocol was amended on Feb. 2, 2011 to allow patients in both study arms to receive the higher dose upon progression.*

Although three deaths may have been associated with the combination treatment, the investigators report that grade 3-5 adverse events were not significantly different between the two arms of the trial.

The study was funded by the National Cancer Institute and AstraZeneca. Disclosures for the individual authors are posted at www.nejm.com.

The NEJM report expands on results presented at the San Antonio Breast Cancer Symposium in December 2012. Dr. Hope Rugo and Dr. William Gradishar, associate editors of The Oncology Report, a publication of Elsevier, discussed the regimen at that meeting in the accompanying video.

*Correction, 8/1/2012: An earlier version of this story misstated the date of FDA approval for the 500-mg dose of fulvestrant.

Everolimus in combination with exemestane is now endorsed on both sides of the Atlantic for the treatment of advanced hormone receptor–positive breast cancer that is also HER2-negative.

Approval by the European Commission, announced by drugmaker Novartis on July 30, closely follows approval by the Food and Drug Administration July 20 and a favorable recommendation by the European Medicines Agency June 21. The EC and the FDA specify that the combination is to be used in patients whose breast cancer has recurred or progressed after treatment with an aromatase inhibitor.

The regulators based their decisions on results of the randomized, placebo-controlled, phase III BOLERO-2 trial. In that study, adding everolimus (Afinitor) to exemestane (Aromasin) increased median progression-free survival from 3.2 to 7.8 months in women whose disease had advanced after treatment with letrozole (Femara) or anastrozole (Arimidex).

Everolimus is the first mTOR inhibitor approved in breast cancer. It also has indications in pancreatic cancer, kidney cancer, and subependymal giant cell astrocytoma.

Results of the BOLERO-II trial were presented in December at the annual San Antonio Breast Cancer Symposium. Dr. Howard Burris, Dr. Hope Rugo, and Dr. William Gradishar, editors of The Oncology Report, discuss these findings in the video below:

Everolimus in combination with exemestane is now endorsed on both sides of the Atlantic for the treatment of advanced hormone receptor–positive breast cancer that is also HER2-negative.

Approval by the European Commission, announced by drugmaker Novartis on July 30, closely follows approval by the Food and Drug Administration July 20 and a favorable recommendation by the European Medicines Agency June 21. The EC and the FDA specify that the combination is to be used in patients whose breast cancer has recurred or progressed after treatment with an aromatase inhibitor.

The regulators based their decisions on results of the randomized, placebo-controlled, phase III BOLERO-2 trial. In that study, adding everolimus (Afinitor) to exemestane (Aromasin) increased median progression-free survival from 3.2 to 7.8 months in women whose disease had advanced after treatment with letrozole (Femara) or anastrozole (Arimidex).

Everolimus is the first mTOR inhibitor approved in breast cancer. It also has indications in pancreatic cancer, kidney cancer, and subependymal giant cell astrocytoma.

Results of the BOLERO-II trial were presented in December at the annual San Antonio Breast Cancer Symposium. Dr. Howard Burris, Dr. Hope Rugo, and Dr. William Gradishar, editors of The Oncology Report, discuss these findings in the video below:

Everolimus in combination with exemestane is now endorsed on both sides of the Atlantic for the treatment of advanced hormone receptor–positive breast cancer that is also HER2-negative.

Approval by the European Commission, announced by drugmaker Novartis on July 30, closely follows approval by the Food and Drug Administration July 20 and a favorable recommendation by the European Medicines Agency June 21. The EC and the FDA specify that the combination is to be used in patients whose breast cancer has recurred or progressed after treatment with an aromatase inhibitor.

The regulators based their decisions on results of the randomized, placebo-controlled, phase III BOLERO-2 trial. In that study, adding everolimus (Afinitor) to exemestane (Aromasin) increased median progression-free survival from 3.2 to 7.8 months in women whose disease had advanced after treatment with letrozole (Femara) or anastrozole (Arimidex).

Everolimus is the first mTOR inhibitor approved in breast cancer. It also has indications in pancreatic cancer, kidney cancer, and subependymal giant cell astrocytoma.

Results of the BOLERO-II trial were presented in December at the annual San Antonio Breast Cancer Symposium. Dr. Howard Burris, Dr. Hope Rugo, and Dr. William Gradishar, editors of The Oncology Report, discuss these findings in the video below: