Impact of use of CDK4/6i and neratinib among patients with HER2 +ve MBC: Results from a real world dataset.

Abstract

e13046 Background: The introduction of anti-HER2 therapy has improved the prognostic outcome of pts with HER2+ve MBC. A phase II trial revealed that among pts with HR+ve/HER2+ve MBC the use of CDK4/6i with anti-HER2 and endocrine therapy was associated with a survival advantage compared to anti-HER2 therapy and chemotherapy. A phase III trial showed that neratinib + capecitabine improved OS compared to lapatinib and capecitabine. With a plethora of new and efficacious anti-HER2 therapy now available the true clinical utility of CDK4/6i and neratinib are undetermined. The objective of this retrospective analysis was to look at the prognostic outcome associated with use of CDK4/6i and neratinib among pts with HER2+ve MBC in the real-world setting. Methods: We utilized a federated network of de-identified health data representing approximately 107 million pt lives available through the TriNetX Research Network. We identified pts with 6511pts with HER2+ve MBC diagnosed since 2015 who were treated with ant-HER2 therapy including trastuzumab, pertuzumab, neratinib, lapatinib, TDM-1 and margetuximab. OS was computed using the Kaplan Meier product limit method. HR+ve status was defined by treatment with endocrine therapy after metastasis, and triple negative (TNBC) status was identified if they did not receive anti-HER2 therapy or endocrine therapy. Results: Mean age was 57.0 yrs. 3679(57.2%) and 2832(42.8%) pts had HR+ve and HR-ve disease, respectively. 2-year OS among pts diagnosed prior to 2015 and during or after 2015 was 79.7% and 82.8%, respectively (p=0.0041). 2-year OS among pts with HR+ve and HR-ve MBC was 87.0% and 75.4%, respectively (p<0.0001). Among pts with HR+ve MBC, 592(16.1%) received a CDK4/6i. Median time to use of CDK4/6i was 4.7m. 2-year OS among pts who did and did not receive a CDK4/6i was 85.1% and 87.5%, respectively (p=0.1844). Median OS among pts who received CDK4/6i within the first year of MBC diagnosis compared to those who received it after the first year of diagnosis was 71.0m and 69.4m, respectively (p=0.0679). No difference in OS was observed among pts with HR+ve disease who had brain mets who did and did not receive CDK4/6i(49.5m vs 54.5m p=0.7335). 327(5.0%) pts received neratinib, of whom 63.9% had HR+ve MBC. 2-year OS among pts who did and did not receive neratinib was 85.1% and 82.6%, respectively(p=0.2366). No difference in 2-year OS was observed among pts who did and did not receive neratinib stratified by HR status and presence of brain metastasis. Conclusions: OS among pts with HER2+ve MBC has significantly improved over time. The use of CDK4/6i among pts with HR+ve/HER2+ve MBC and use of neratinib among pts with HER2+ve MBC did not impact OS.