Trastuzumab-lapatinib as neoadjuvant therapy for HER2-positive early breast cancer: Survival analyses of the CHER-Lob trial. (August 2021)

• Record Type: Journal Article
• Authors: Guarneri, Valentina; Dieci, Maria V.; Griguolo, Gaia; Miglietta, Federica; Girardi, Fabio; Bisagni, Giancarlo; Generali, Daniele G.; Cagossi, Katia; Sarti, Samanta; Frassoldati, Antonio; Gianni, Lorenzo; Cavanna, Luigi; Pinotti, Graziella; Musolino, Antonino; Piacentini, Federico; Cinieri, Saverio; Prat, Aleix; Conte, PierFranco
• Is Part Of: European journal of cancer. Volume 153(2021)
• Page Start: 133
• Page End: 141
• Publication Date: 2021-08
• Subjects: HER2-positive breast cancer -- Neoadjuvant treatment -- Lapatinib -- Trastuzumab -- Escalation; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2021.05.018
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Aim: 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. Methods: 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. Results: 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). Conclusions: 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. Trial registration: NCT00429299. Highlights: The Cher-LOB study confirmed pathologic complete response to be strongly prognostic in human epidermal growth factor receptor 2 (HER2)+ breast cancer. A signal for a better outcome with dual HER2-blockade over trastuzumab was observed. Tumour-infiltrating lymphocytes were confirmed to be strongly prognostic in HER2+ early breast cancer. Luminal A PAM50 subtype had a positive and independent association with recurrence-free survival.