FDA approves neratinib regimen for HER2-positive metastatic breast cancer
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The FDA approved neratinib as part of combination treatment of HER2-positive metastatic breast cancer, according to the agent’s manufacturer.
Neratinib (Nerlynx, Puma Biotechnology) — an irreversible pan-HER tyrosine kinase inhibitor — already had been approved for single-agent extended adjuvant treatment of adults with early-stage HER2-positive breast cancer after adjuvant trastuzumab (Herceptin, Genentech)-based therapy.
The latest approval applies to neratinib’s use in combination with capecitabine for treatment of adults with advanced or metastatic HER2-positive breast cancer who received at least two prior anti-HER2-based regimens in the metastatic setting.
The FDA based the new indication on results of the randomized phase 3 NALA trial, which included 621 patients with metastatic HER2-positive breast cancer who received two or more prior anti-HER2-based regimens for metastatic disease.
Researchers assigned 307 patients to neratinib dosed at 240 mg orally once daily on days 1 to 21 in combination with oral capecitabine dosed at 750 mg/m2 twice daily on days 1 to 14 for each 21-day cycle. The other 314 patients received lapatinib (Tykerb, GlaxoSmithKline) dosed at 1,250 mg orally once daily on days 1 to 21 in combination with oral capecitabine dosed at 1,000 mg/m2 twice daily on days 1 to 14 for each 21-day cycle.
Treatment continued until disease progression or unacceptable toxicity.
PFS assessed by blinded independent central review and OS served as the primary efficacy outcomes. Key secondary outcomes included objective response rate and duration of response.
Results showed a statistically significant PFS improvement among patients assigned neratinib-capecitabine (HR = 0.76; 95% CI, 0.63-0.93). A higher percentage of patients assigned the neratinib regimen remained progression free at 12 months (29% vs. 15%) and 24 months (12% vs. 3%).
Researchers also reported longer median OS with the neratinib regimen, but the difference did not reach statistical significance (21 months vs. 18.7 months; HR = 0.88; 95% CI, 0.72-1.07).
ORR (32.8% vs. 26.7%) and median duration of response (8.5 months vs. 5.6 months) favored the neratinib-capecitabine combination.
The most common adverse events among patients assigned the neratinib regimen included diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, weight loss, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment and muscle spasms.
The most common grade 3 or grade 4 adverse events included diarrhea, nausea, vomiting, fatigue and decreased appetite.
“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, CEO and president of Puma Biotechnology, said in a company-issued press release. “Based on the results of our NALA data, we believe Nerlynx could be a promising therapeutic opportunity for these patients.”