Abstract P4-21-20: Lapatinib after pertuzumab and ado-trastuzumab emtansine in metastatic HER2-positive breast cancer

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Abstract Background: Lapatinib (L) is approved in combination with capecitabine for patients with trastuzumab-resistant HER2-positive metastatic breast cancer (MBC) and in combination with letrozole for HER2-positive and ER/PR-receptor-positive MBC for whom hormonal therapy is indicated. However, there are no data on the activity of L in patients who received prior pertuzumab (P) and ado-trastuzumab emtansine (TDM-1), now included as standard first and second line therapies. The goal of this study was to assess the efficacy of L in routine clinical practice in a contemporary patient population that received prior P and/or TDM-1. Methods: We identified all patients with trastuzumab-resistant HER2-positive MBC who received L-based therapy (n=570) between 2003 and 2016 through a departmental database at MD Anderson Cancer Center and reviewed the medical records of each patient to confirm treatment sequencing and outcome. Of these patients, we identified a target cohort who received L after prior P or TDM-1 (n=34). Analysis used Kaplan-Meier statistics. Results: Of the 34 patients identified as the target cohort with prior P and/or TDM-1 exposure, 29 patients were available for outcome analysis since 5 patients were started on L-based treatment within 4 months of this analysis. In the comparison cohort (n=536) who had received L-based therapy without prior P and/or TDM-1 exposure, 445 patients were available for outcome analysis. Table 1: ResultsCharacteristicsTarget Cohort (N=34)Comparison Cohort (N=536)Median Age, years (range)51 (31,78)52 (24,85)Median lines of metastatic therapy prior to L, n (range)2.5(1-6)1 (0-12)Discontinuation of L due to toxicity, n (%)1 (3)54 (10)CBR, % (95% CI)58 (39, 79)78(74, 84)Median TTP, months (95% CI)4.9 (3.0, 7.6)5.7 (0.0, 82.3) De novo7.4 (2.9, NR)5.9 (5.5, 9.0) Recurrent4.5 (2.9, 8.3)6.7 (6.0, 7.8)Median OS, months (95% CI)23.9 (20.5, NR)25.8 (23.1, 30.6) De Novo26.1 (23.9, NR)27.8 (22.8, 36.9) Recurrent20.5 (12.7, NR)25.5 (22.5, 30.7)Abbreviations: NR – not reached; CI – confidence interval In we display the patient characteristics and results. Clinical benefit rate (CBR), defined as complete or partial response or stable disease > 6 months, was 58% (95% CI, 39%, 79%) for the target cohort and 78% (74%, 84%) for the comparison cohort. In the target cohort, nearly 25% (n=8) had received > 3 lines of therapy and in the comparison cohort only 10% (n=71) had received > 3 lines of therapy. The median duration on L was 4.9 months (range 0.7-19.2) in the target cohort and 5.6 months (range 0.0-82.3) in the comparison cohort. In both cohorts, median TTP and OS were longer in patients with de novo disease compared to patients with disease recurrence. Conclusions: In the target cohort with prior P and TDM-1, nearly one third of patients received L for > 6 months and over half the patients obtained clinical benefit for > 6 months with no significant toxicity. This suggests clinically relevant benefit to L in a contemporary population of patients who have received prior P and TDM-1. However, clinical benefit and median duration on L were decreased in the target cohort versus the comparison cohort, which may reflect heavier pretreatment. Citation Format: Báez-Vallecillo L, Singareeka Raghavendra A, Hess K, Moulder SL, Tripathy D, Valero V, Murthy RK. Lapatinib after pertuzumab and ado-trastuzumab emtansine in metastatic HER2-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-20.