PARP-inhibitors for BRCA1/2-related advanced HER2-negative breast cancer: A meta-analysis and GRADE recommendations by the Italian Association of Medical Oncology
Federica Miglietta,
Michela Cinquini,
Maria Vittoria Dieci,
Laura Cortesi,
Carmen Criscitiello,
Filippo Montemurro,
Lucia Del Mastro,
Alberto Zambelli,
Laura Biganzoli,
Alessia Levaggi,
Chiara Delle Piane,
Caterina Marchiò,
Massimo Calabrese,
Lucio Fortunato,
Pierfrancesco Franco,
Bruno Meduri,
Veronica Andrea Fittipaldo,
Stefania Gori
Affiliations
Federica Miglietta
Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy; Corresponding author. Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.
Michela Cinquini
Istituto di Ricerche Farmacologiche Mario Negri IRCCS., Laboratory of Methodology of Sistematic Reviews and Guidelines production; Department of Oncology, Milano, Italy
Maria Vittoria Dieci
Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
Laura Cortesi
Department of Oncology and Hematology Azienda Ospedaliero-Universitaria di Modena, Italy
Carmen Criscitiello
European Institute of Oncology IRCCS, Milan, Italy; University of Milan, Milan, Italy
Filippo Montemurro
Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
Lucia Del Mastro
Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine and Medical Specialities, School of Medicine, University of Genova, Genova, Italy
Alberto Zambelli
Department of Biomedical Sciences, Humanitas University, Milan, Italy; IRCCS Humanitas Research Hospital, Milan, Italy
Laura Biganzoli
Medical Oncology Division, Hospital of Prato, Prato, Italy
Alessia Levaggi
Department of Oncology, Sant'Andrea Hospital, La Spezia, Italy
Chiara Delle Piane
Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
Caterina Marchiò
Candiolo Cancer Institute FPO-IRCCS, Candiolo, Italy; Department of Medical Sciences, University of Turin, Turin, Italy
Massimo Calabrese
Senologia Diagnostica, IRCCS-Ospedale Policlinico San Martino - Genova, Italy
Lucio Fortunato
Centro di Senologia - Azienda Ospedaliera San Giovanni-Addolorata, Roma, Italy
Pierfrancesco Franco
Department of Translational Medicine (DIMET), University of Eastern Piedmont, Novara, Italy
Bruno Meduri
Radioterapia - Azienda ospedaliera-Universitaria di Modena, Modena, Italy
Veronica Andrea Fittipaldo
Istituto di Ricerche Farmacologiche Mario Negri IRCCS., Laboratory of Methodology of Sistematic Reviews and Guidelines production; Department of Oncology, Milano, Italy
Stefania Gori
Medical Oncology Unit, Sacro Cuore - Don Calabria Hospital, Cancer Care Center, Negrar, Italy
Background: Approximately 5–10% of unselected breast cancer (BC) patients retain a hereditary predisposition related to a germline mutation in BRCA1/2 genes. The poly-ADP ribose polymerase (PARP)-inhibitors olaparib and talazoparib have been granted marketing authorization by both FDA and EMA for adults with BRCA1/2 germline mutations and HER2-negative (HER2-) advanced BC based on the results from the phase III OlympiAd and EMBRACA trials. Methods: The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer addressed two critical clinical questions, adopting the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach and the Evidence to Decision framework (EtD), to develop recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related triple-negative (clinical question 1) and hormone receptor-positive (HR+)/HER2- (clinical question 2) advanced BC. Results: Two studies were eligible (OlympiAd and EMBRACA). For both clinical questions, the Panel judged the benefit/harm balance probably in favor of the intervention, given the favorable impact in terms of PFS, ORR, and QoL at an acceptable cost in terms of toxicity; the overall certainty of the evidence was low. The panel's final recommendations were conditional in favor of PARP-inhibitors over single-agent chemotherapy in both HR+/HER2-and triple-negative BC. Finally, the Panel identified and discussed areas of uncertainty calling for further exploration. Conclusions: The Panel of AIOM BC Clinical Practice Guideline provided clinical recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related HER2-advanced BC by adopting the GRADE methodology.
