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Top Line: Which tyrosine kinase inhibitor is best for metastatic, HER2+ breast cancer?
The Study: NALA was a phase 3 trial comparing lapatinib + capecitabine (LC) with neratinib + capecitabine (NC) for women with metastatic HER2+ breast cancer after two prior HER2-targeted regimens. Over 600 patients were enrolled. Among those, roughly ⅓ had received prior trastuzumab, pertuzumab, and T-DM1, and 16% had stable, asymptomatic brain metastases. In comparison, prior therapy with all three drugs was required for HER2CLIMB and nearly 50% of those patients had brain metastases. The NC arm showed superior progression-free survival at 1 year (29%) compared to LC (15%), and a clear separation in the PFS curves emerged at 6 months after enrollment. There was no significant difference, though, in overall survival. The PFS benefit appeared to be driven by increased response rate with NC (32.8% vs 26.7%) as well as a longer duration of response (8.5 vs 5.6 months). The PFS benefit was also most apparent among the subset of patients with triple-positive disease. In patients with brain metastases, the cumulative rate of intervention for CNS disease was lower with NC (22.8%) than with LC (29.2%). On the down side, diarrhea was a frequent adverse event and happened twice as much with NC (24%) than with LC (12.5%).
TBL: Neratinib is superior to lapatinib when paired with capecitabine for women with metastatic HER2+ breast cancer. | Saura, J Clin Oncol 2020