Breast cancer incidence in patients with BRCA-related advanced ovarian cancer receiving olaparib-based maintenance therapy: A pooled analysis from phase III clinical trials.

Authors

null

Michele Bartoletti

Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy

Michele Bartoletti , Marcella Montico , Roberta Mazzeo , Marco De Scordilli , Lucia Musacchio , Emilio Lucia , Giorgio Giorda , Samuele Massarut , Martina Urbani , Gianmaria Miolo , Alessandra Viel , Mattia Garutti , Lucia Da Ros , Simona Scalone , Milena Nicoloso , Serena Corsetti , Roberto Sorio , Domenica Lorusso , Sandro Pignata , Fabio Puglisi

Organizations

Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy, Clinical Trial Office, Scientific Direction, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy, Department of Medicine, University of Udine, Udine, Italy, Udine, Italy, Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy, Unit of Gynecologic Oncology Surgery, IRCCS CRO Aviano, National Cancer Institute, Aviano, Italy, Aviano, Italy, Dipartimento di Oncologia Chirurgica Ginecologica, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy, Aviano, Italy, CRO - National Cancer Institute, Aviano, Italy, Department of Radiology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy, Centro di Riferimento Oncologico di Avano (CRO) IRCCS, Aviano, Italy, CRO Aviano, National Cancer Institute, Aviano, Italy, Dipartimento di Oncologia Medica, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy, Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy, MITO and Centro di Riferimento Oncologico-IRCCS, Aviano, Italy, Fondazione Policlinico Gemelli IRCCS, Rome, Italy, Department of Urology and Gynecology, Istituto Nazionale Tumori di Napoli IRCCS Fondazione G Pascale, Naples, Italy

Research Funding

No funding received

Background: As the prognosis of BRCA-related advanced ovarian cancer (AOC) continues to improve thanks to the introduction of targeted therapies like poly ADP-ribose polymerase inhibitors (PARPi) and bevacizumab, the occurrence of second primary tumors, in particular breast cancer (BC), is assumed to be more common. Despite this, data on the incidence of BC in this population are poor and guidelines for BC screening or risk reducing strategies are lacking. Methods: Published data from recent PARPi-based, phase III clinical trials involving germline BRCA mutated AOC were reviewed and analyzed. Only studies in which the incidence of at least one second primary solid tumor was reported were included. Cases of second primary BC cancers were pooled to calculate cumulative incidence according to the median follow-up period for each trial. 95% confidence interval (CI) was considered. Results: Four trials (SOLO1, PAOLA1, SOLO2 and SOLO3) involving 1186 germline BRCA 1-2 mutated AOC patients were included (BRCA1, n = 816; BRCA2, n = 360; BRCA1 + BRCA2, n = 4; missing, n = 6). In all trials, patients were randomized to receive olaparib +/- bevacizumab (n = 788) versus placebo or standard therapies (n = 398). Median age at diagnosis of AOC was 56 years (range, 29-87). With a follow-up ranging from 3.9 months to 5 years, 16 new cases of BC were recorded, 10 in PARPi-based arms and 6 in control arms. Only two patients had a previous history of BC. The total cumulative incidence of BC was 1.37% (95% CI, 0.77-2.18), while cumulative incidences were 1.26% (95% CI, 0.61-2.31) and 1.51% (95% CI, 0.55-3.25) in PARPi-based arms and control arms, respectively. In a sensitivity analysis excluding the SOLO3 trial with the shortest follow-up, the total cumulative incidence was 1.63% (95% CI, 0.92-2.67). Other 20 cases of second primary solid tumors were registered, including 4 cases of non-small cell lung cancer. Conclusions: Patients with germline BRCA-related AOC receiving PARPi-based maintenance therapy can be reassured about the risk of second primary BC and intensive screening should be avoided at least in early treatment phase. More data with long term follow-up are needed.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gynecologic Cancer

Track

Gynecologic Cancer

Sub Track

Ovarian Cancer

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 5566)

DOI

10.1200/JCO.2022.40.16_suppl.5566

Abstract #

5566

Poster Bd #

444

Abstract Disclosures