The journey of patients affected by metastatic hormone receptor-positive/HER2-negative breast cancer from CDK 4/6 inhibitors to second-line treatment: A real-world analysis of 701 patients enrolled in the GIM14/BIOMETA study

Chiara Molinelli; Marco Bruzzone; Eva Blondeaux; Tommaso Ruelle; Chiara Lanzavecchia; Michelino De Laurentiis; Stefania Russo; Ferdinando Riccardi; Valentina Sini; Francesco Cognetti; Grazia Arpino; Alessandra Fabi; Palma Pugliese; Elena Collovà; Andrea Fontana; Fabio Puglisi; Claudia Bighin; Matteo Lambertini; Lucia Del Mastro

doi:10.1016/j.ejca.2024.115113

The journey of patients affected by metastatic hormone receptor-positive/HER2-negative breast cancer from CDK 4/6 inhibitors to second-line treatment: A real-world analysis of 701 patients enrolled in the GIM14/BIOMETA study

Eur J Cancer. 2024 Nov 4:213:115113. doi: 10.1016/j.ejca.2024.115113. Online ahead of print.

Authors

Chiara Molinelli¹, Marco Bruzzone², Eva Blondeaux², Tommaso Ruelle³, Chiara Lanzavecchia³, Michelino De Laurentiis⁴, Stefania Russo⁵, Ferdinando Riccardi⁶, Valentina Sini⁷, Francesco Cognetti⁸, Grazia Arpino⁹, Alessandra Fabi¹⁰, Palma Pugliese¹¹, Elena Collovà¹², Andrea Fontana¹³, Fabio Puglisi¹⁴, Claudia Bighin¹⁵, Matteo Lambertini¹⁶, Lucia Del Mastro¹⁷

Affiliations

¹ Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy; Department of Medical Oncology, UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. Electronic address: https://twitter.com/@ChiaraMolinelli.
² U. O. Epidemiologia Clinica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
³ Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy; Department of Medical Oncology, UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
⁴ Division of Breast Medical Oncology, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Naples, Italy.
⁵ Department of Oncology, ASU FC University Hospital, Udine, Italy.
⁶ U.O.C. Oncologia, AORN Cardarelli, Napoli, Italy.
⁷ UOSD Centro Oncologico S. Spirito e Nuovo Regina Margherita, ASL Roma 1, Rome, Italy.
⁸ Division of Medical Oncology 1, Regina Elena National Cancer Institute, Roma, Italy.
⁹ Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
¹⁰ Precision Medicine Unit in Senology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Romania.
¹¹ SC Oncologia ASST Lariana Ospedale S. Anna, Como, Italy.
¹² Medical Oncology Unit, ASST Ovest Milanese Legnano, Milan, Italy.
¹³ Medical Oncology Unit 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
¹⁴ Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, Aviano, PN, Italy; Department of Medicine, University of Udine, Udine, Italy, CRO Aviano, National Cancer Institute, IRCCS, Aviano, PN, Italy.
¹⁵ Medical Oncology Department 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
¹⁶ Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy; Department of Medical Oncology, UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. Electronic address: https://twitter.com/@matteolambe.
¹⁷ Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy; Department of Medical Oncology, UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. Electronic address: [email protected].

PMID: 39536433
DOI: 10.1016/j.ejca.2024.115113

Abstract

Purpose: The aim of this study was to evaluate the effectiveness of CDK 4/6 inhibitors (CDK 4-6i) according to HER2 status (low/zero), and endocrine resistance/sensitivity, as well as the efficacy of second-line treatments, in a large real-world cohort.

Methods: The GIM14/BIOMETA study (NCT02284581) is a retrospective/prospective study of the Gruppo Italiano Mammella evaluating treatment patterns and survival outcomes in patients with metastatic breast cancer (MBC). We retrieved data on patients with hormone receptor-positive/HER2-negative MBC receiving first-line CDK 4/6i.

Results: Among 3832 patients enrolled in the GIM14-BIOMETA study, 701 were eligible. At a median follow-up of 24.80 months, no significant differences were found between HER2-zero and HER2-low subgroups in terms of first-line time to treatment discontinuation (TTD) (26.16 months [IQR 12.84-NR] vs. 27.60 months [IQR 12.12-64.44], p = 0.972) or overall survival (OS) (mOS>60 months for both groups, p = 0.398). Median TTD was 33.24 months (IQR 16.32-NR) for the endocrine sensitive subgroup, 19.92 months (IQR 8.88-51.24) for the secondary endocrine resistant subgroup and 17.40 months (IQR 7.44-24.72) for the primary endocrine resistant subset, respectively (p < 0.001). Among 239 patients receiving second-line treatment, no significant difference (p = 0.188) was found in terms of second-line TTD between those treated with capecitabine (6.11 months, IQR 2.96-11.47), taxane-based chemotherapy (5.06 months, IQR 2.99-9.99), everolimus plus exemestane (5.39 months, IQR 2.53-9.03) or fulvestrant (6.44 months, IQR 3.38-NR).

Conclusions: Endocrine therapy plus CDK 4/6i represents an effective treatment, regardless of HER2 status (low/zero). Second-line agents did not differ significantly in terms of TTD. Endocrine resistant cancers exhibit poor response to CDK 4/6i.

Keywords: CDK 4/6 inhibitors; HER2-low; Luminal breast cancer; Metastatic breast cancer; Second-line treatment.