FDA Approves Supplemental NDA for Neratinib in Metastatic HER2-Positive Breast Cancer

The FDA has approved a supplemental New Drug Application (NDA) for neratinib (Nerlynx) in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have previously received 2 or more anti—HER2-based regimens in the metastatic setting, according to a press release issued by the manufacturer Puma Biotechnology, Inc.¹

The decision was supported by data from theNALA trial(NCT01808573) that were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, which demonstrated that the combination resulted in a 24% reduction in the risk of disease progression or death compared with lapatinib (Tykerb) and capecitabine.

A prior approval allowed for the use of neratinib as extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy.

“Although there have been many new treatment options for patients with HER2-positive breast cancer, patients still need additional treatment options once they progress,” Alan H. Auerbach, chief executive officer and president, Puma Biotechnology, Inc, said in a statement. “Based on the results of our NALA data, we believe Nerlynx could be a promising therapeutic opportunity for these patients.”

NALA was a randomized, multicenter, open-label phase III clinical trial evaluating 621 patients who were randomized to receive neratinib 240 mg orally once daily on days 1 through 21 in combination with capecitabine 750 mg/m²given orally twice daily on days 1 through 14 for each 21-day cycle (n = 307) or lapatinib 1250 mg orally once daily on days 1 through 21 in combination with capecitabine 1000 mg/m²given orally twice daily on days 1 through 14 for each 21-day cycle (n = 314).

Investigators reported that patients in the neratinib arm demonstrated a statistically significant improvement in progression-free survival (PFS) compared with patients who received lapatinib plus capecitabine (HR, 0.76; 95% CI, 0.63-0.93;P= .0059). When the PFS rate was reviewed at 12 months, PFS was found to be 29% (95% CI, 23%-35%) for patients who received neratinib plus capecitabine versus 15% (95% CI, 10%-20%) for patients who received lapatinib plus capecitabine; the PFS rate at 24 months was 12% (95% CI, 7%-18%) versus 3% (95% CI, 1%-8%), respectively.

Median overall survival was 21 months (95% CI, 17.7-23.8) for patients who received neratinib in combination with capecitabine compared with 18.7 months (95% CI, 15.5-21.2) for patients who received lapatinib in combination plus capecitabine (HR, 0.88; 95% CI, 0.72-1.07;P= .2086). The objective response rate was 32.8% (95% CI, 27.1%-38.9%) versus 26.7% (95% CI, 21.5%-32.4%), respectively. Median duration of response was 8.5 months (95% CI, 5.6-11.2) versus 5.6 months (95% CI, 4.2-6.4), respectively.

Approximately 20% to 25% of breast cancer tumors overexpress the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death.

“Together with the NALA investigators around the world, I am pleased to see the FDA approval of Nerlynx for the treatment of advanced HER2-positive metastatic breast cancer,” said co-investigator Adam M. Brufsky, MD, PhD, of Magee-Womens Hospital and the Hillman Cancer Center at the University of Pittsburgh Medical Center, in a statement.

Reference:

Puma Biotechnology receives U.S. FDA approval of supplemental new drug application for neratinib to treat HER2-positive metastatic breast cancer [news release]. Los Angeles, CA: Puma Biotechnology, Inc.; February 26, 2020. https://bit.ly/2TfqDmc. Accessed February 26, 2020.