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Puma's Nerlynx Demonstrates Survival Gains in Early-Stage Breast Cancer Patients

NEW YORK – Treatment with Puma Biotechnology's neratinib (Nerlynx) following adjuvant or neoadjuvant trastuzumab (Genentech's Herceptin) resulted in an overall survival benefit for some women with HER2-positive, hormone receptor-positive, early-stage breast cancer, according to a final efficacy analysis in the Phase III ExteNET study.

The ExteNET trial randomized a total of 2,840 patients with HER2-positive, early-stage breast cancer to receive either neratinib or placebo after trastuzumab. Based on the invasive disease-free survival benefit that the agent demonstrated in earlier readouts from the trial, neratinib has secured regulatory approvals in multiple countries, including in the US, for this patient population. However, data pertaining to overall survival benefit — one of the trial's key secondary endpoints — was not yet mature in 2017, when the US Food and Drug Administration first approved the agent for this patient population.

Now, the longer-term, final efficacy analysis, published this week in the journal Clinical Breast Cancer, demonstrated a 2.1 percent overall survival benefit at eight years for patients with HR-positive disease who received neratinib within one year of receiving adjuvant trastuzumab compared to those on placebo.

In addition to final overall survival results, the Clinical Breast Cancer manuscript details patients' central nervous system recurrence rates and several noteworthy subgroup analyses. In the neratinib group, only 0.7 percent of patients experienced CNS disease recurrence after five years versus 2.1 percent of patients in the placebo group.

"The trend toward lower CNS involvement is a very important consideration, given the profound impact of CNS metastasis on future prognosis," Hope Rugo of the University of California, San Francisco, one of the authors on the Clinical Breast Cancer study, said in a statement.

A notable subpopulation analysis within ExteNET involved patients with HR-positive disease who did not experience a pathologic complete response following their initial neoadjuvant trastuzumab treatment but received neratinib within one year. In this subgroup, considered to be at higher risk of recurrence, the invasive disease-free survival benefit at five years was 7.4 percent with neratinib compared to placebo, and the overall survival benefit at eight years with neratinib was 9.1 percent versus placebo.

"This newly published study provides consistent and durable benefits of neratinib in a subset of HER2-positive, early-stage breast cancer patients who are considered to be at greater risk of relapse," Arlene Chan of the Breast Cancer Research Center Western Australia and the lead author of the paper, said in a statement. "The benefits demonstrated are meaningful in all endpoints evaluated … and thus should help guide future clinical decisions."

In addition to the early-stage disease indication, Puma garnered FDA approval for neratinib earlier this year as a treatment for patients with advanced or metastatic HER2-positive breast cancer who have previously received two or more anti-HER2 therapies. The approval was supported by the results of the Phase III NALA trial.

The firm is also evaluating the agent in a broader, tumor-agnostic basket trial, dubbed SUMMIT, for patients with various cancers harboring HER2 or EGFR exon 18 mutations. The SUMMIT trial is evaluating responses to neratinib, either as a monotherapy or in combination with chemotherapy, fulvestrant (AstraZeneca's Faslodex), or fulvestrant and trastuzumab.