Additional Chemotherapy Improves Survival in Women with Residual Disease After Neoadjuvant Chemotherapy

May 2016, Vol 7, No 4

It is not clear how to treat residual disease after neoadjuvant therapy in patients with early HER2-negative breast cancer. Additional chemotherapy with capecitabine improved survival in this group of patients, according to a large Japanese study presented by lead investigator Masakazu Toi, MD, PhD, Professor, Breast Surgery, Kyoto Hospital, Japan, at the 2015 San Antonio Breast Cancer Symposium.

Adjuvant capecitabine after an incomplete response to neoadjuvant therapy led to a 5-year disease-free survival rate of 74.1% versus 67.7% for patients who did not receive adjuvant chemotherapy after surgery. The 5-year overall survival (OS) rate was 89.2% with adjuvant capecitabine versus 83.9% without the addition of capecitabine.

“We showed that OS was significantly improved by capecitabine adjuvant therapy for nonpathologic complete response or node-positive patients after neoadjuvant chemotherapy,” said Dr Toi. “The balance of benefit and toxicity would favor the use of capecitabine in the postneoadjuvant chemotherapy situation, but prediction for the therapeutic benefit needs further study.”

Benefits Seen with Capecitabine

A subgroup analysis demonstrated a consistent survival benefit that favored adjuvant capecitabine, regardless of patient age, hormone receptor (HR) status, pathologic grade, or type of neoadjuvant chemotherapy, he added.

The multicenter, randomized trial initiated by the Japan Breast Cancer Research Group addressed the question of whether additional systemic therapy after surgery could improve survival in the presence of residual disease or positive nodes after neoadjuvant therapy.

Patients with stage I to IIIb, HER2-­negative breast cancer received standard neoadjuvant therapy using an anthracycline- or taxane-based regimen. After surgery, patients with residual invasive disease were randomized to 6 months of adjuvant capecitabine or to standard therapy (ie, endocrine therapy for HR-positive disease and no further therapy for the remainder of the patients).

When a preplanned interim analysis of 2 years of enrollment was complete, the data and safety monitoring committee recommended stopping the trial because of the benefit of capecitabine. Dr Toi presented data on 885 patients who were randomized to either arm.

The median patient age was 48 years, 58% of patients were premenopausal, 63% had HR-positive tumors, 38% had 1 to 3 HR-positive lymph nodes, and 22% had 4 HR-positive lymph nodes.

Of the patients in the capecitabine arm, 45% completed therapy as planned, 32% required dose reductions, and 22.5% discontinued treatment.

Grade 4 neutropenia occurred in 6.6% of the capecitabine arm versus in 1.6% of the control arm, and grade 3 to 4 diarrhea occurred in 3% versus 0.4% of the arms, respectively. Hand-foot syndrome of all grades was reported in 72.3% of the capecitabine arm, and the rate of grade 3 hand-foot syndrome was 10.9%.

The 3-year disease-free survival rates were 82.8% in the capecitabine arm and 74% in the control arm, representing a 30% improvement with capeci­tabine. The 3-year OS rates were 94% with capecitabine and 89.2% without it, for a 40% reduction in mortality favoring capecitabine.

Press conference moderator Virginia G. Kaklamani, MD, DSc, Leader, Breast Cancer Program, Cancer Therapy and Research Center, the University of Texas Health Science Center at San Antonio, said that the study focused on a group of patients for whom the best treatment is unclear.

“We know that in patients with a pathologic complete response to neoadjuvant chemotherapy, these women do very well,” Dr Kaklamani said. “If they have residual disease, they don’t do very well, but we really don’t know what to do with these patients.”

“This study shows that giving a totally different chemotherapy—capecita­bine—that patients had not been exposed to before can help them live longer,” she said.

The cost of an additional 6 months of chemotherapy could be an issue. If insurers do not pay for this, many women would not be able to afford it, Dr Kaklamani noted.

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