Paclitaxel Matches New Drugs as First-Line Breast Cancer Therapy

CHICAGO – Two fairly new and expensive drugs for breast cancer were no more effective or safer than a drug that has been used for this disease for over a decade, finds a phase III cooperative group trial among nearly 800 women with chemotherapy-naive locally recurrent or metastatic disease.

The trial pitted the newer nab-paclitaxel (Abraxane) and ixabepilone (Ixempra) against the older paclitaxel (Taxol) as a control, each given weekly, along with bevacizumab (Avastin) given every 2 weeks, as first-line therapy.

Trial results reported at the annual meeting of the American Society of Clinical Oncology showed that progression-free survival was not superior with nab-paclitaxel and was in fact inferior with ixabepilone, translating to a 53% higher risk of progression or death relative to paclitaxel, first author Dr. Hope S. Rugo reported in a press briefing.

Moreover, rates of grade 3 or worse adverse events were higher with both of the newer agents than with the old stand-by.

"These data suggest that similar patients could be appropriately treated with weekly paclitaxel," said Dr. Rugo, professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco.

"Interestingly, ixabepilone is an epothilone where preclinical and some clinical data suggest an ability to reverse resistance to the microtubule inhibitors like paclitaxel, and nab-paclitaxel has similar data," she added. "However, in this chemotherapy-naive population, these results showed equivalency or inferiority."

Susan London/IMNG Medical Media

"These are all good drugs, these are all major-league baseball players. I want them all on my team," asserted press briefing moderator Dr. Nicholas Vogelzang, chair and medical director, Developmental Therapeutics Committee, US Oncology, Comprehensive Cancer Centers of Nevada. "And when they are used to treat breast cancer, a patient should be considered for all of them, perhaps in different sequences for different patients."

The trial’s findings do not preclude use of at least nab-paclitaxel in selected patients similar to those studied or in other treatment settings, according to Dr. Rugo.

"Based on our data, it’s very unlikely that [nab-paclitaxel] is superior to paclitaxel, but it could be used as an alternative in patients who had a reason not to receive paclitaxel," such as an allergy to cremophor (paclitaxel’s solvent), or diabetes making it hard to tolerate the steroids needed as premedication, she said. Also, the drug is effective in patients with later-stage metastatic breast cancer or with cancers that have progressed on other taxanes.

Finally, nab-paclitaxel is a useful alternative in the context of drug shortages. "In the setting where paclitaxel is not readily available, nab-paclitaxel could clearly be used in its place," she said.

Of note, however, data have shown that nab-paclitaxel given at a lower dose of 100 mg/m² – one-third lower than the dose used in the trial – is less toxic. Therefore, "in patients in whom nab-paclitaxel is chosen ... we should be using the 100 mg/m² dose," Dr. Rugo recommended.

The trial, formally known as CALGB 40502/NCCTG N063H and sponsored by the National Cancer Institute, randomized 799 patients to open-label treatment with one of the three chemotherapies – paclitaxel (90 mg/m² weekly, the most commonly used dosage schedule), nab-paclitaxel (150 mg/m² weekly), or ixabepilone (16 mg/m² weekly) – plus bevacizumab every 2 weeks.

All chemotherapy was given on a 3-weeks-on, 1-week-off schedule. Patients who had a response or stable disease after six cycles could stop chemotherapy and continue with the bevacizumab alone.

With a median follow-up of 12 months, analyses showed that progression-free survival was no better with nab-paclitaxel (9.2 months; hazard ratio, 1.19; P = .12) and was actually worse with ixabepilone (7.6 months; hazard ratio, 1.53; P less than .0001) than with paclitaxel (10.6 months), Dr. Rugo reported.

The overall rate of grade 3 or worse adverse events was 55% with paclitaxel, compared with 79% with nab-paclitaxel and 59% with ixabepilone.

The rate of grade 3 or worse nonhematologic adverse events was significantly higher with the newer agents than with the older one. "We saw increased peripheral neuropathy in the experimental arms as compared with the control arms as well," Dr. Rugo noted. The rate of grade 3 or worse hematologic events was significantly higher with nab-paclitaxel and significantly lower with ixabepilone.

The findings are likely to remain relevant despite the Food and Drug Administration’s withdrawal of approval for bevacizumab, according to Dr. Rugo. "Interestingly, in our study, we obviously don’t have a control arm without bevacizumab, but the progression-free survival in the control arm was almost identical to ECOG 2100," which compared paclitaxel with and without bevacizumab. "And I think for that reason, it’s unlikely that there would be a big difference if you redid the whole study without bevacizumab," she said.

Dr. Rugo said she receives research funding from Abraxis BioScience, Bristol-Myers Squibb, and Roche/Genentech. Dr. Vogelzang said he is a consultant to Amgen, AVEO, Bayer, Celgene(U), Dendreon, Eisai, GE Healthcare, Genentech, GlaxoSmithKline, Johnson & Johnson, Keryx, Medscape, Novartis, Oncogenex, Pfizer, and Wilex; he receives honoraria from Amgen, Bayer, Clinical Care Options, Genentech, Imedex, Lilly, Lippincott, Williams, and Wilkins, Medscape, Novartis, Onyx, Pfizer, and Veridex; and he receives research funding from Algeta, Pfizer, Progenics, and Tokai Pharmaceuticals.

CHICAGO – Two fairly new and expensive drugs for breast cancer were no more effective or safer than a drug that has been used for this disease for over a decade, finds a phase III cooperative group trial among nearly 800 women with chemotherapy-naive locally recurrent or metastatic disease.

The trial pitted the newer nab-paclitaxel (Abraxane) and ixabepilone (Ixempra) against the older paclitaxel (Taxol) as a control, each given weekly, along with bevacizumab (Avastin) given every 2 weeks, as first-line therapy.

Trial results reported at the annual meeting of the American Society of Clinical Oncology showed that progression-free survival was not superior with nab-paclitaxel and was in fact inferior with ixabepilone, translating to a 53% higher risk of progression or death relative to paclitaxel, first author Dr. Hope S. Rugo reported in a press briefing.

Moreover, rates of grade 3 or worse adverse events were higher with both of the newer agents than with the old stand-by.

"These data suggest that similar patients could be appropriately treated with weekly paclitaxel," said Dr. Rugo, professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco.

"Interestingly, ixabepilone is an epothilone where preclinical and some clinical data suggest an ability to reverse resistance to the microtubule inhibitors like paclitaxel, and nab-paclitaxel has similar data," she added. "However, in this chemotherapy-naive population, these results showed equivalency or inferiority."

Susan London/IMNG Medical Media

"These are all good drugs, these are all major-league baseball players. I want them all on my team," asserted press briefing moderator Dr. Nicholas Vogelzang, chair and medical director, Developmental Therapeutics Committee, US Oncology, Comprehensive Cancer Centers of Nevada. "And when they are used to treat breast cancer, a patient should be considered for all of them, perhaps in different sequences for different patients."

The trial’s findings do not preclude use of at least nab-paclitaxel in selected patients similar to those studied or in other treatment settings, according to Dr. Rugo.

"Based on our data, it’s very unlikely that [nab-paclitaxel] is superior to paclitaxel, but it could be used as an alternative in patients who had a reason not to receive paclitaxel," such as an allergy to cremophor (paclitaxel’s solvent), or diabetes making it hard to tolerate the steroids needed as premedication, she said. Also, the drug is effective in patients with later-stage metastatic breast cancer or with cancers that have progressed on other taxanes.

Finally, nab-paclitaxel is a useful alternative in the context of drug shortages. "In the setting where paclitaxel is not readily available, nab-paclitaxel could clearly be used in its place," she said.

Of note, however, data have shown that nab-paclitaxel given at a lower dose of 100 mg/m² – one-third lower than the dose used in the trial – is less toxic. Therefore, "in patients in whom nab-paclitaxel is chosen ... we should be using the 100 mg/m² dose," Dr. Rugo recommended.

The trial, formally known as CALGB 40502/NCCTG N063H and sponsored by the National Cancer Institute, randomized 799 patients to open-label treatment with one of the three chemotherapies – paclitaxel (90 mg/m² weekly, the most commonly used dosage schedule), nab-paclitaxel (150 mg/m² weekly), or ixabepilone (16 mg/m² weekly) – plus bevacizumab every 2 weeks.

All chemotherapy was given on a 3-weeks-on, 1-week-off schedule. Patients who had a response or stable disease after six cycles could stop chemotherapy and continue with the bevacizumab alone.

With a median follow-up of 12 months, analyses showed that progression-free survival was no better with nab-paclitaxel (9.2 months; hazard ratio, 1.19; P = .12) and was actually worse with ixabepilone (7.6 months; hazard ratio, 1.53; P less than .0001) than with paclitaxel (10.6 months), Dr. Rugo reported.

The overall rate of grade 3 or worse adverse events was 55% with paclitaxel, compared with 79% with nab-paclitaxel and 59% with ixabepilone.

The rate of grade 3 or worse nonhematologic adverse events was significantly higher with the newer agents than with the older one. "We saw increased peripheral neuropathy in the experimental arms as compared with the control arms as well," Dr. Rugo noted. The rate of grade 3 or worse hematologic events was significantly higher with nab-paclitaxel and significantly lower with ixabepilone.

The findings are likely to remain relevant despite the Food and Drug Administration’s withdrawal of approval for bevacizumab, according to Dr. Rugo. "Interestingly, in our study, we obviously don’t have a control arm without bevacizumab, but the progression-free survival in the control arm was almost identical to ECOG 2100," which compared paclitaxel with and without bevacizumab. "And I think for that reason, it’s unlikely that there would be a big difference if you redid the whole study without bevacizumab," she said.

Dr. Rugo said she receives research funding from Abraxis BioScience, Bristol-Myers Squibb, and Roche/Genentech. Dr. Vogelzang said he is a consultant to Amgen, AVEO, Bayer, Celgene(U), Dendreon, Eisai, GE Healthcare, Genentech, GlaxoSmithKline, Johnson & Johnson, Keryx, Medscape, Novartis, Oncogenex, Pfizer, and Wilex; he receives honoraria from Amgen, Bayer, Clinical Care Options, Genentech, Imedex, Lilly, Lippincott, Williams, and Wilkins, Medscape, Novartis, Onyx, Pfizer, and Veridex; and he receives research funding from Algeta, Pfizer, Progenics, and Tokai Pharmaceuticals.

CHICAGO – Two fairly new and expensive drugs for breast cancer were no more effective or safer than a drug that has been used for this disease for over a decade, finds a phase III cooperative group trial among nearly 800 women with chemotherapy-naive locally recurrent or metastatic disease.

The trial pitted the newer nab-paclitaxel (Abraxane) and ixabepilone (Ixempra) against the older paclitaxel (Taxol) as a control, each given weekly, along with bevacizumab (Avastin) given every 2 weeks, as first-line therapy.

Trial results reported at the annual meeting of the American Society of Clinical Oncology showed that progression-free survival was not superior with nab-paclitaxel and was in fact inferior with ixabepilone, translating to a 53% higher risk of progression or death relative to paclitaxel, first author Dr. Hope S. Rugo reported in a press briefing.

Moreover, rates of grade 3 or worse adverse events were higher with both of the newer agents than with the old stand-by.

"These data suggest that similar patients could be appropriately treated with weekly paclitaxel," said Dr. Rugo, professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco.

"Interestingly, ixabepilone is an epothilone where preclinical and some clinical data suggest an ability to reverse resistance to the microtubule inhibitors like paclitaxel, and nab-paclitaxel has similar data," she added. "However, in this chemotherapy-naive population, these results showed equivalency or inferiority."

Susan London/IMNG Medical Media

"These are all good drugs, these are all major-league baseball players. I want them all on my team," asserted press briefing moderator Dr. Nicholas Vogelzang, chair and medical director, Developmental Therapeutics Committee, US Oncology, Comprehensive Cancer Centers of Nevada. "And when they are used to treat breast cancer, a patient should be considered for all of them, perhaps in different sequences for different patients."

The trial’s findings do not preclude use of at least nab-paclitaxel in selected patients similar to those studied or in other treatment settings, according to Dr. Rugo.

"Based on our data, it’s very unlikely that [nab-paclitaxel] is superior to paclitaxel, but it could be used as an alternative in patients who had a reason not to receive paclitaxel," such as an allergy to cremophor (paclitaxel’s solvent), or diabetes making it hard to tolerate the steroids needed as premedication, she said. Also, the drug is effective in patients with later-stage metastatic breast cancer or with cancers that have progressed on other taxanes.

Finally, nab-paclitaxel is a useful alternative in the context of drug shortages. "In the setting where paclitaxel is not readily available, nab-paclitaxel could clearly be used in its place," she said.

Of note, however, data have shown that nab-paclitaxel given at a lower dose of 100 mg/m² – one-third lower than the dose used in the trial – is less toxic. Therefore, "in patients in whom nab-paclitaxel is chosen ... we should be using the 100 mg/m² dose," Dr. Rugo recommended.

The trial, formally known as CALGB 40502/NCCTG N063H and sponsored by the National Cancer Institute, randomized 799 patients to open-label treatment with one of the three chemotherapies – paclitaxel (90 mg/m² weekly, the most commonly used dosage schedule), nab-paclitaxel (150 mg/m² weekly), or ixabepilone (16 mg/m² weekly) – plus bevacizumab every 2 weeks.

All chemotherapy was given on a 3-weeks-on, 1-week-off schedule. Patients who had a response or stable disease after six cycles could stop chemotherapy and continue with the bevacizumab alone.

With a median follow-up of 12 months, analyses showed that progression-free survival was no better with nab-paclitaxel (9.2 months; hazard ratio, 1.19; P = .12) and was actually worse with ixabepilone (7.6 months; hazard ratio, 1.53; P less than .0001) than with paclitaxel (10.6 months), Dr. Rugo reported.

The overall rate of grade 3 or worse adverse events was 55% with paclitaxel, compared with 79% with nab-paclitaxel and 59% with ixabepilone.

The rate of grade 3 or worse nonhematologic adverse events was significantly higher with the newer agents than with the older one. "We saw increased peripheral neuropathy in the experimental arms as compared with the control arms as well," Dr. Rugo noted. The rate of grade 3 or worse hematologic events was significantly higher with nab-paclitaxel and significantly lower with ixabepilone.

The findings are likely to remain relevant despite the Food and Drug Administration’s withdrawal of approval for bevacizumab, according to Dr. Rugo. "Interestingly, in our study, we obviously don’t have a control arm without bevacizumab, but the progression-free survival in the control arm was almost identical to ECOG 2100," which compared paclitaxel with and without bevacizumab. "And I think for that reason, it’s unlikely that there would be a big difference if you redid the whole study without bevacizumab," she said.

Dr. Rugo said she receives research funding from Abraxis BioScience, Bristol-Myers Squibb, and Roche/Genentech. Dr. Vogelzang said he is a consultant to Amgen, AVEO, Bayer, Celgene(U), Dendreon, Eisai, GE Healthcare, Genentech, GlaxoSmithKline, Johnson & Johnson, Keryx, Medscape, Novartis, Oncogenex, Pfizer, and Wilex; he receives honoraria from Amgen, Bayer, Clinical Care Options, Genentech, Imedex, Lilly, Lippincott, Williams, and Wilkins, Medscape, Novartis, Onyx, Pfizer, and Veridex; and he receives research funding from Algeta, Pfizer, Progenics, and Tokai Pharmaceuticals.