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

The FDA has approved a supplemental New Drug Application for neratinib 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.

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.