The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

According to results of a phase 3 study presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, the combination of neratinib plus capecitabine was associated with an improvement in progression-free survival (PFS) compared with lapatinib plus capecitabine in women with HER2-positive metastatic breast cancer who had received prior treatment with at least 2 different HER2-targeted agents in the metastatic setting.

In the randomized, open-label NALA study ( Identifier: NCT01808573), patients with HER2-positive metastatic breast cancer who had received prior treatment for metastatic disease with 2 or more HER2-directed agents were randomly assigned in a 1:1 ratio to receive neratinib (240 mg orally once daily), an irreversible panHER tyrosine kinase inhibitor (TKI), in combination with capecitabine or lapatinib (1250 mg orally once daily), a reversible HER1/HER2 TKI, plus capecitabine.  Patients who had received prior treatment with capecitabine, neratinib, lapatinib or any other HER2-targeted TKI were excluded from the study. The coprimary end points of the study were PFS and overall survival (OS). Secondary study end points included objective response rate (ORR), clinical benefit rate (CBR), duration of response (DoR), time to intervention for symptomatic metastatic central nervous system disease, as well as safety and health outcomes assessments.

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Of the 621 patients who underwent randomization, 307 and 314 patients were assigned to the neratinib and lapatinib arms, respectively. Approximately 80% of patients in both arms had visceral disease, and approximately one-third of those in each arm had received prior treatment with trastuzumab, pertuzumab, and T-DM1.

There was a 24% decrease in risk of disease progression for patients receiving neratinib-based therapy (HR, 0.76; 95% CI, 0.63–0.93; P =.0059).

Significant improvements in CBR (45% vs 36%; P =.0328) and time to intervention of symptomatic CNS disease (P =.043) were noted for patients receiving neratinib-containing vs lapatinib-containing therapy. In addition, DoR was also significantly improved for those receiving neratinib/capecitabine compared with lapatinib/capecitabine (HR, 0.50; 95% CI 0.33–0.74; P =.0004).

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However,  OS (P =.2086), as well as ORR in patients with measurable disease (33% vs 27%; P =.1201) were not significantly different between the 2 study arms.

No new safety signals were observed in this study. No notable differences were observed in a comparison of treatment-emergent adverse events occurring in the arms with the exception of grade 3 diarrhea, which was observed in 24.4% of patients treated with neratinib-based therapy compared with 12.5% for patients treated with lapatinib/capecitabine. Interestingly, fewer patients receiving neratinib (10.9%) compared with lapatinib (14.5%) discontinued these agents due to a treatment-emergent adverse event.

In his concluding remarks, Adam Brufsky, MD, PhD, Hillman Cancer Center, University of Pittsburgh Medical Center, Pennsylvania, who presented these results on behalf of the NALA investigators, stated that “these trial results suggest that neratinib plus capecitabine is an effective option for treating progressive HER2-positive metastatic breast cancer.”

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.


Saura C, Oliveira M, Feng Y-H, et al. Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: Findings from the multinational, randomized, phase III NALA trial. Presented at: 2019 American Society of Clinical Oncology Annual Meeting. May 31-June 4, 2019; Chicago, IL. Abstract 1002.