SABCS: CREATE-X – Capecitabine is efficacious against residual HER2-negative breast cancer

SAN ANTONIO – Adjuvant capecitabine improves outcomes in women with HER2-negative breast cancer who still have invasive disease after neoadjuvant chemotherapy, according to findings of the CREATE-X trial reported at the San Antonio Breast Cancer Symposium.

“Patients with pathologic residual invasive disease after neoadjuvant chemotherapy have a higher risk for relapse,” said presenting author Dr. Masakazu Toi, a professor at Kyoto University Hospital in Japan, and founder and senior director of the Japan Breast Cancer Research Group (JBCRG). But “it is unclear whether postoperative systemic chemotherapy following neoadjuvant chemotherapy is able to prolong survival.”

The phase III trial was conducted among 910 patients with early breast cancer in Japan and Korea who still had positive nodes or didn’t achieve a pathologic complete response after receipt of neoadjuvant chemotherapy that included an anthracycline, a taxane, or both. They were randomized to open-label adjuvant capecitabine (Xeloda) or no capecitabine, in addition to standard therapy.

Results of a preplanned 2-year interim analysis, reported in a session and related press briefing, showed that the risk of disease-free survival events was 30% lower and the risk of death was 40% lower among women given capecitabine than among counterparts not given the drug, prompting early stopping of the trial.

The disease-free survival results were similar in subgroup analyses. In particular, benefit was similar in patients with triple-negative disease, who historically haven’t fared well on this drug.

“The balance of benefit and toxicity would favor the use of capecitabine in [this] post–neoadjuvant chemotherapy situation, but prediction for therapeutic benefit needs to be investigated further,” Dr. Toi concluded. “The cost-effectiveness analysis will be carried out soon,” he added.

Press briefing moderator Dr. Virginia Kaklamani, codirector of the San Antonio Breast Cancer Symposium, as well as professor of medicine in the division of hematology/oncology at the University of Texas, San Antonio, and leader of the Breast Cancer Program, Cancer Therapy & Research Center there, wondered if the results are practice changing.

“On Monday morning, when I see a patient who has residual disease after neoadjuvant chemotherapy, what do I tell her?” she asked.

“I think we need to take care of the reimbursement issue,” Dr. Toi replied, referring to the current lack of U.S. Food and Drug Administration approval of capecitabine for this indication. “But personally, I would like to consider this treatment.”

In the session where the findings were presented, some attendees expressed skepticism about the observed benefit of capecitabine, given previous studies.

This benefit may have been due in part to the fact that in CREATE-X, capecitabine was given largely because it does not have cross-resistance with anthracyclines and taxanes, Dr. Toi speculated.

Attendee Dr. Steven Vogl, an oncologist at the Montefiore Medical Center in New York, proposed that the findings may have different implications for women with estrogen receptor–positive versus triple-negative disease, based on both their likelihood of pathologic complete response (pCR)and the prognostic impact of that response.

“I put it to you that really what this tells us is if we have a triple-negative patient who doesn’t achieve pCR after good neoadjuvant therapy, this [capecitabine] is probably a reasonable option, even though it’s quite toxic, and certainly should be explored further,” he said. “I’m not sure I would go home and treat my ER-positive patients who don’t get a pCR with capecitabine based on this study.”

In the trial, the 2-year disease-free survival rate – the trial’s primary endpoint – was 82.8% with capecitabine and 74.0% without it. The estimated 5-year rates were 74.1% and 67.7%, respectively (hazard ratio, 0.70; P = .005).

Furthermore, the 2-year overall survival rate was 94% with capecitabine and 89.2% without it. The estimated 5-year rates were 89.2% and 83.9%, respectively (HR, 0.60; P less than .01).

Patients in the capecitabine arm were more likely to experience grade 3 or worse neutropenia (7% vs. 2%) and diarrhea (3% vs. less than 1%). And 11% developed grade 3 hand-foot syndrome. However, these toxicities were manageable, according to the investigators.

Dr. Toi disclosed that he receives a research grant from Chugai Pharmaceutical Company. The trial was supported by a grant from Specified Nonprofit Corporation – Advanced Clinical Research Organization (ACRO) and other donations to the Japan Breast Cancer Research Group.

SAN ANTONIO – Adjuvant capecitabine improves outcomes in women with HER2-negative breast cancer who still have invasive disease after neoadjuvant chemotherapy, according to findings of the CREATE-X trial reported at the San Antonio Breast Cancer Symposium.

“Patients with pathologic residual invasive disease after neoadjuvant chemotherapy have a higher risk for relapse,” said presenting author Dr. Masakazu Toi, a professor at Kyoto University Hospital in Japan, and founder and senior director of the Japan Breast Cancer Research Group (JBCRG). But “it is unclear whether postoperative systemic chemotherapy following neoadjuvant chemotherapy is able to prolong survival.”

The phase III trial was conducted among 910 patients with early breast cancer in Japan and Korea who still had positive nodes or didn’t achieve a pathologic complete response after receipt of neoadjuvant chemotherapy that included an anthracycline, a taxane, or both. They were randomized to open-label adjuvant capecitabine (Xeloda) or no capecitabine, in addition to standard therapy.

Results of a preplanned 2-year interim analysis, reported in a session and related press briefing, showed that the risk of disease-free survival events was 30% lower and the risk of death was 40% lower among women given capecitabine than among counterparts not given the drug, prompting early stopping of the trial.

The disease-free survival results were similar in subgroup analyses. In particular, benefit was similar in patients with triple-negative disease, who historically haven’t fared well on this drug.

“The balance of benefit and toxicity would favor the use of capecitabine in [this] post–neoadjuvant chemotherapy situation, but prediction for therapeutic benefit needs to be investigated further,” Dr. Toi concluded. “The cost-effectiveness analysis will be carried out soon,” he added.

Press briefing moderator Dr. Virginia Kaklamani, codirector of the San Antonio Breast Cancer Symposium, as well as professor of medicine in the division of hematology/oncology at the University of Texas, San Antonio, and leader of the Breast Cancer Program, Cancer Therapy & Research Center there, wondered if the results are practice changing.

“On Monday morning, when I see a patient who has residual disease after neoadjuvant chemotherapy, what do I tell her?” she asked.

“I think we need to take care of the reimbursement issue,” Dr. Toi replied, referring to the current lack of U.S. Food and Drug Administration approval of capecitabine for this indication. “But personally, I would like to consider this treatment.”

In the session where the findings were presented, some attendees expressed skepticism about the observed benefit of capecitabine, given previous studies.

This benefit may have been due in part to the fact that in CREATE-X, capecitabine was given largely because it does not have cross-resistance with anthracyclines and taxanes, Dr. Toi speculated.

Attendee Dr. Steven Vogl, an oncologist at the Montefiore Medical Center in New York, proposed that the findings may have different implications for women with estrogen receptor–positive versus triple-negative disease, based on both their likelihood of pathologic complete response (pCR)and the prognostic impact of that response.

“I put it to you that really what this tells us is if we have a triple-negative patient who doesn’t achieve pCR after good neoadjuvant therapy, this [capecitabine] is probably a reasonable option, even though it’s quite toxic, and certainly should be explored further,” he said. “I’m not sure I would go home and treat my ER-positive patients who don’t get a pCR with capecitabine based on this study.”

In the trial, the 2-year disease-free survival rate – the trial’s primary endpoint – was 82.8% with capecitabine and 74.0% without it. The estimated 5-year rates were 74.1% and 67.7%, respectively (hazard ratio, 0.70; P = .005).

Furthermore, the 2-year overall survival rate was 94% with capecitabine and 89.2% without it. The estimated 5-year rates were 89.2% and 83.9%, respectively (HR, 0.60; P less than .01).

Patients in the capecitabine arm were more likely to experience grade 3 or worse neutropenia (7% vs. 2%) and diarrhea (3% vs. less than 1%). And 11% developed grade 3 hand-foot syndrome. However, these toxicities were manageable, according to the investigators.

Dr. Toi disclosed that he receives a research grant from Chugai Pharmaceutical Company. The trial was supported by a grant from Specified Nonprofit Corporation – Advanced Clinical Research Organization (ACRO) and other donations to the Japan Breast Cancer Research Group.

SAN ANTONIO – Adjuvant capecitabine improves outcomes in women with HER2-negative breast cancer who still have invasive disease after neoadjuvant chemotherapy, according to findings of the CREATE-X trial reported at the San Antonio Breast Cancer Symposium.

“Patients with pathologic residual invasive disease after neoadjuvant chemotherapy have a higher risk for relapse,” said presenting author Dr. Masakazu Toi, a professor at Kyoto University Hospital in Japan, and founder and senior director of the Japan Breast Cancer Research Group (JBCRG). But “it is unclear whether postoperative systemic chemotherapy following neoadjuvant chemotherapy is able to prolong survival.”

The phase III trial was conducted among 910 patients with early breast cancer in Japan and Korea who still had positive nodes or didn’t achieve a pathologic complete response after receipt of neoadjuvant chemotherapy that included an anthracycline, a taxane, or both. They were randomized to open-label adjuvant capecitabine (Xeloda) or no capecitabine, in addition to standard therapy.

Results of a preplanned 2-year interim analysis, reported in a session and related press briefing, showed that the risk of disease-free survival events was 30% lower and the risk of death was 40% lower among women given capecitabine than among counterparts not given the drug, prompting early stopping of the trial.

The disease-free survival results were similar in subgroup analyses. In particular, benefit was similar in patients with triple-negative disease, who historically haven’t fared well on this drug.

“The balance of benefit and toxicity would favor the use of capecitabine in [this] post–neoadjuvant chemotherapy situation, but prediction for therapeutic benefit needs to be investigated further,” Dr. Toi concluded. “The cost-effectiveness analysis will be carried out soon,” he added.

Press briefing moderator Dr. Virginia Kaklamani, codirector of the San Antonio Breast Cancer Symposium, as well as professor of medicine in the division of hematology/oncology at the University of Texas, San Antonio, and leader of the Breast Cancer Program, Cancer Therapy & Research Center there, wondered if the results are practice changing.

“On Monday morning, when I see a patient who has residual disease after neoadjuvant chemotherapy, what do I tell her?” she asked.

“I think we need to take care of the reimbursement issue,” Dr. Toi replied, referring to the current lack of U.S. Food and Drug Administration approval of capecitabine for this indication. “But personally, I would like to consider this treatment.”

In the session where the findings were presented, some attendees expressed skepticism about the observed benefit of capecitabine, given previous studies.

This benefit may have been due in part to the fact that in CREATE-X, capecitabine was given largely because it does not have cross-resistance with anthracyclines and taxanes, Dr. Toi speculated.

Attendee Dr. Steven Vogl, an oncologist at the Montefiore Medical Center in New York, proposed that the findings may have different implications for women with estrogen receptor–positive versus triple-negative disease, based on both their likelihood of pathologic complete response (pCR)and the prognostic impact of that response.

“I put it to you that really what this tells us is if we have a triple-negative patient who doesn’t achieve pCR after good neoadjuvant therapy, this [capecitabine] is probably a reasonable option, even though it’s quite toxic, and certainly should be explored further,” he said. “I’m not sure I would go home and treat my ER-positive patients who don’t get a pCR with capecitabine based on this study.”

In the trial, the 2-year disease-free survival rate – the trial’s primary endpoint – was 82.8% with capecitabine and 74.0% without it. The estimated 5-year rates were 74.1% and 67.7%, respectively (hazard ratio, 0.70; P = .005).

Furthermore, the 2-year overall survival rate was 94% with capecitabine and 89.2% without it. The estimated 5-year rates were 89.2% and 83.9%, respectively (HR, 0.60; P less than .01).

Patients in the capecitabine arm were more likely to experience grade 3 or worse neutropenia (7% vs. 2%) and diarrhea (3% vs. less than 1%). And 11% developed grade 3 hand-foot syndrome. However, these toxicities were manageable, according to the investigators.

Dr. Toi disclosed that he receives a research grant from Chugai Pharmaceutical Company. The trial was supported by a grant from Specified Nonprofit Corporation – Advanced Clinical Research Organization (ACRO) and other donations to the Japan Breast Cancer Research Group.