On February 25, the U.S. Food and Drug Administration (FDA) approved neratinib (Nerlynx), a tyrosine kinase inhibitor, in combination with capecitabine for adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2–based regimens in the metastatic setting.
Efficacy of neratinib with capecitabine was investigated in NALA, a phase III, randomized, multicenter, open-label clinical trial of 621 patients with metastatic HER2-positive breast cancer who received two or more prior anti–HER2-based regimens in the metastatic setting. Patients were randomly assigned 1:1 to receive 240 mg of neratinib orally once daily on days 1–21 with 750 mg/m2 of capecitabine given orally twice daily on days 1 to 14 for each 21-day cycle (n = 307), or 1,250 mg of lapatinib orally once daily on days 1–21 with 1,000 mg/m2 of capecitabine given orally twice daily on days 1 to 14 for each 21-day cycle (n = 314). Patients were treated until disease progression or unacceptable toxicity.
The primary efficacy outcome measures were progression-free survival (assessed by a blinded independent central review per Response Evaluation Criteria in Solid Tumors, version 1.1) and overall survival. Key secondary outcome measures were objective response rate and duration of response.
Progression-Free and Overall Survival
Median progression-free survival was 5.6 months (95% confidence interval [CI] = 4.9–6.9) for patients who received neratinib/capecitabine and 5.5 months (95% CI = 4.3–5.6) for those who received lapatinib/capecitabine (hazard ratio [HR] = 0.76, 95% CI = 0.63–0.93, P = .0059). The 12-month progression-free survival rate was 29% (95% CI = 23–35) vs 15% (95% CI = 10–20).
Median overall survival was 21 months (95% CI = 17.7–23.8) for patients treated with neratinib/capecitabine vs 18.7 months (95% CI = 15.5–21.2) for those treated with lapatinib/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) vs 26.7% (95% CI = 21.5–32.4), respectively. Median response duration was 8.5 (95% CI = 5.6–11.2) vs 5.6 months (95% CI = 4.2–6.4).
The most common adverse reactions of any grade (> 5%) in the neratinib/capecitabine arm were diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, weight decrease, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment, and muscle spasms. The most frequently reported grade 3 or 4 adverse reactions were diarrhea, nausea, vomiting, fatigue, and decreased appetite.
The recommended neratinib dose for advanced or metastatic breast cancer is 240 mg (six tablets) given orally once daily with food on days 1 to 21 of a 21-day cycle plus capecitabine (750 mg/m2 given orally twice daily) on days 1 to 14 of a 21-day cycle until disease progression or unacceptable toxicity.