Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published.
A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine®).
A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4–53.1) and OS was 105.4 months (95% CI: 82.7–not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found.
MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor’s characteristics.
Clinical trial registration
This study is registered under NCT02408536 on ClinicalTrials.gov.
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The datasets used and analyzed during the current study are available from the corresponding authors on reasonable request.
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The authors are grateful to Gelsomina Iovane, Margherita Tambaro and Angela Maria Trujillo for data management.
A specific funding was received for this work. The research leading to these results has received funding from AIRC under IG 2016 – ID. 18921 and IG 2021 – ID. 25932 projects – P.I. SP and CO-2018–12367051 (Ministero della Salute) P.I SP; Ricerca Corrente grant M2/7 from Ministero della Salute to DC, Ricerca Corrente from Ministero della Salute to SP.
DL reports research funding from Clovis, GSK and MSD, personal interests with AstraZeneca, Clovis Oncology, GSK, Pharmamar, MSD and financial interests with Clovis, Genmab, GSK, MSD. Board of Directors, GCIG (Gynecologic Cancer Inter Group). FR reports honoraria from GSK, Pharmamar, Clovis, MSD and Roche. VS reports honoraria from GSK, PharmaMar, Roche, MSD, EISAI, Clovis, Oncology, AstraZeneca. FP reports honoraria for educational and advisory activity from Incyte, GSK, Eli Lilly, Ipsen, Astellas, AstraZeneca, Roche, BMS, Bayer, Clovis, Pierre Fabre and grants for clinical trials to his institution from Roche, Astra Zeneca, Pfizer, MSD, Bayer, Incyte Taiho, Janssen, Exelixis, Ailenor, Daiichi Sankyo. GS reports research support from MSD and honoraria from Clovis Oncology. Consultant for Tesaro and Johnson & Johnson. SP reports honoraria from AstraZeneca, MSD, Roche, Pfizer, Clovis, GSK, Pharmamar and research funding from MSD, Roche, Astrazeneca and Pfizer. LM, DC, MB, LA, NSL, GC, SG, GV, CP, AS, DR, MDS, VC, FF, GFZ, VL, VG, CC, VT, MD, VDV, SS and DP have nothing to disclose.
Ethics approval and consent to participate
This study was approved by the ethics committee of the National Cancer Institute of Naples (22/14 OSS) and the ethics committees of the participating centers, and it was conducted in accordance with the Declaration of Helsinki. The study participants gave written informed consent.
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Musacchio, L., Califano, D., Bartoletti, M. et al. Clinical characteristics and molecular aspects of low-grade serous ovarian and peritoneal cancer: a multicenter, observational, retrospective analysis of MITO Group (MITO 22). Br J Cancer 127, 1479–1486 (2022). https://doi.org/10.1038/s41416-022-01897-1