Trastuzumab-lapatinib as neoadjuvant therapy for HER2-positive early breast cancer: Survival analyses of the CHER-Lob trial.

The Cher-LOB randomised phase II study showed that the combination of lapatinib-trastuzumab plus chemotherapy increases pathologic complete response (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. Here, we report the post hoc survival analysis as per treatment arm, pCR and biomarkers. The Cher-LOB study randomised 121 patients with human epidermal growth factor receptor 2-positive, stage II-IIIA breast cancer. A specific protocol to collect recurrence-free survival (RFS) and overall survival (OS) data was designed. Tumour-infiltrating lymphocytes (TILs) and PAM50-intrinsic subtyping were evaluated at baseline. At 9-year median follow-up, a trend towards RFS improvement with lapatinib-trastuzumab over trastuzumab was observed (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.18-1.05). Combining treatment arms, pCR was significantly associated with both RFS (HR 0.12, 95% CI 0.03-0.49) and OS (HR 0.12, 95% CI 0.03-0.49). TILs were significantly associated with RFS (HR = 0.978 for each 1% increment). Luminal-A subtype was a significant and independent predictor of improved RFS as compared with other PAM50-based intrinsic subtypes at the multivariate analysis including the most relevant clinicopathologic variables (HR 0.29, 95% CI 0.09-0.94, p = 0.040). Cher-LOB trial survival analysis confirmed the prognostic role of pCR and TILs and showed a signal for a better outcome with lapatinib-trastuzumab over trastuzumab. NCT00429299.

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Conflict of interest statement V.G. reports personal fees from Roche, Novartis, Eli Lilly and MSD outside the submitted work. D.G.G. reports personal fees from Roche, Novartis, Eli Lilly and Pierre Fabre, all outside the submitted work. A.F. reports personal fees from Roche, Novartis, Pfizer, Lilly, Daiichi and Seagen, all outside the submitted work. L.G. reports honoraria for lectures and ad boards from Lilly, Pfizer, Novartis and AstraZeneca, all outside the submitted work, reports travel accommodation and expenses from Novartis and Daiichi Sankyo and is an uncompensated member of the Olympia steering committee. A.M. reports grants and personal fees from Roche and Eisai; personal fees from Lilly, MacroGenics and Novartis and grants from Pfizer, all outside the submitted work. S.C. reports personal fees from Lilly Oncology outside the submitted work. A.P. reports grants and personal fees from Roche, AstraZeneca, Daiichi Sankyo, Merck Sharp & Dohme (MSD), PUMA Biotechnology, Novartis and Nanostring Technologies, personal fees from Seattle Genetics, Lilly, Pfizer, Guardant Health, Oncolytics Biotech and Abbvie, all outside the submitted work, and a patent (WO2018/103834A1) licensed to Nanostring Technologies, a patent (WO/2018/096191) issued. M.V.D. reports personal fees from Lilly, Genomic Health, Novartis and Celgene, all outside the submitted work. P.F.C. reports personal fees from Novartis, Eli Lilly, AstraZeneca, Tesaro, BMS and Roche, all outside the submitted work. All remaining authors have declared no conflicts of interest.