Background

The primary endpoint hypotheses for the phase 3 Study 309/KEYNOTE-775 were formally tested at interim analysis 1; LEN + pembro demonstrated statistically significant improvements in PFS and OS vs TPC in pts with aEC. ORR was higher with LEN + pembro vs TPC. We report updated analyses of this study.

Methods

Pts with aEC and 1 prior platinum-based chemotherapy regimen (up to 2 if 1 was given in the neoadjuvant/adjuvant setting) were randomized (1:1) to receive LEN 20 mg orally QD + pembro 200 mg IV Q3W or TPC (doxorubicin at 60 mg/m² IV Q3W or paclitaxel at 80 mg/m² IV QW [3 wks on; 1 wk off]). Randomization was stratified by mismatch repair (MMR) status; pts with proficient (p)MMR tumors were further stratified by ECOG PS, geographic region, and history of pelvic irradiation. We report final pre-specified OS, PFS and ORR (assessed by blinded independent central review per RECIST v1.1; in randomized pts), and safety (in pts who received treatment) (data cutoff: March 1, 2022). Analyses are descriptive.

Results

827 Pts (pMMR, n = 697; deficient MMR, n = 130) were randomized to LEN + pembro (n = 411) or TPC (n = 416). Median follow-up in all-comers was 18.7 mo (LEN + pembro) and 12.2 mo (TPC). Median PFS remained longer with LEN + pembro vs TPC in pMMR aEC (6.7 vs 3.8 mo) and in all-comers (7.3 vs 3.8 mo). Median OS remained longer with LEN + pembro vs TPC in pMMR aEC (18.0 vs 12.2 mo) and in all-comers (18.7 vs 11.9 mo) (Table), despite some pts in the TPC arm receiving subsequent LEN + pembro (pMMR, 10.0%; all-comers; 8.7%). Grade ≥ 3 TEAEs occurred in 90% of pts with LEN + pembro and 74% of pts with TPC.

Conclusions

Consistent with the primary analysis, LEN + pembro continued to demonstrate clinically meaningful improvement in PFS, OS, and ORR vs TPC in pts with aEC (pMMR and all-comers) who received prior platinum therapy. Safety was generally consistent with the primary analysis and previous studies. Table: 525MO

Clinical trial identification

NCT03517449.

Editorial acknowledgement

Medical writing support was provided by Irene Minkina, PhD, of Oxford PharmaGenesis Inc., Newtown, PA, USA, with funding by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

V. Makker: Financial Interests, Institutional, Funding, Study funding: Merck, Eisai, Clovis, Karyopharm, AstraZeneca; Financial Interests, Institutional, Funding, Study support: Zymeworks; Non-Financial Interests, Principal Investigator: Merck; Non-Financial Interests, Advisory Role: Eisai, Clovis, Novartis, Lilly, Gsk, Karyopharm, Iteos, Faeth. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GSK, Pfizer, Takeda, BIOCAD, Immunogen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca, Tesaro; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche; Non-Financial Interests, Other, Sterring committee member Clinical Guidelines: ESMO; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO( Alleanza contro il tumore ovarico). A. Casado Herraez: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Eisai , Merck, PharmaMar; Financial Interests, Personal, Other, support for attending major international oncological conferences -virtually or face to face meetings: PharmaMar, Lilly, Roche, AstraZeneca, Merck, GSK; Financial Interests, Institutional, Research Grant: PharmaMar. B.J. Monk: Financial Interests, Personal, Other, Consultant Honoraria: Agenus, Akeso Bio, Amgen, AstraZeneca, Eisai , Elevar, Genmab/Seagen, GOG Foundation, Gradilis, ImmunoGen, Karyopharm, Iovance, Macrogenics, Mersana, Novocure, Myriad, OncoC4, Pieris, Pfizer, Puma, Regeneron, VBL, Sorrento; Financial Interests, Personal, Other, Speaker/Consultant Honoraria: Aravive, Bayer, Clovis, Roche/Genentech, Tesaro/GSK; Financial Interests, Personal, Other, Speaker/Consulant Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Principal Investigator, Consultant: Us Oncology Research. H. Mackay: Financial Interests, Personal, Advisory Board: Merck, GSK, AstraZeneca. A.D. Santin: Financial Interests, Institutional, Research Grant: Puma, Immunomedics, Gilead, Synthon, Genentech, Tesaro, Eisai; Financial Interests, Personal, Other, Personal fees: Eisai, Tesaro. D.S. Miller: Financial Interests, Personal, Advisory Role: Eisai, AstraZeneca, Karyopharm Therapeutics, Incyte, Merck Sharpe & Dohme, Asymmetric Therapeutics, Boston Biomedical Research Institute, Tarveda Therapeutics , Myriad Genetic Laboratories, GlaxoSmithKline, Abbvie, Incyte, EMD Serono, Seattle Genetics, Clinical Education Alliance, Eisai, iTEOS Therapeutics, Novocure, Novartis, Immunogen, Agenus; Financial Interests, Institutional, Research Grant: US Biotest, Advenchen Laboratories, Tesaro , Xenetic Biosciences, Advaxis, Janssen, Aeterna Zentaris, TRACON Pharma, Pfizer, Immunogen, Mateon Therapeutics, Merck , AstraZeneca, Millenium Pharamceuticals, Aprea AB , Regeneron, NVision, Leap Therapeutics, Novartis , Syros Pharmaceuticals , Karyopharm , Agenus , Akesobio, EMD Serono, Incyte . R.G. Moore: Financial Interests, Institutional, Research Grant: Angle plc; Financial Interests, Personal, Other, Consulting: Fujirebio Diagnostics Inc. . S.E. Baron-Hay: Financial Interests, Institutional, Research Grant: Eisai, Merck Sharpe & Dohme (Australia Pty Ltd), Pfizer; Financial Interests, Personal, Research Grant: AstraZeneca Australia; Financial Interests, Personal, Other, Honoraria: Amgen, NovartisvPharmaceuticals Australia Pty Ptd, Eli Lilly Australia, Roche, Merck Sharp and Dohme (Australia Pty Ltd). I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, Adaptimmune, Eisai, Sutro; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1; Non-Financial Interests, Other, President: Gineco. R. Shapira-Frommer: Financial Interests, Personal, Advisory Board: MSD, Neopharm; Financial Interests, Personal, Invited Speaker: MSD, BMS, Astra Zenaca, Medison, Novartis, Roche; Financial Interests, Personal, Other, consultation: Msdison; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Invited Speaker: AstraZeneca, MSD. K. Ushijima: Financial Interests, Institutional, Research Grant: MSD, Eisai. K. Yonemori: Financial Interests, Personal, Invited Speaker: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fujifilm Pharma, MSD, Ono; Financial Interests, Personal, Advisory Board: Novartis, Eisai , AstraZeneca, Chugai , Takeda, Genmab, OncXerna; Financial Interests, Institutional, Research Grant: MSD, Daiichi-Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Seagen, Haihe. E.M. Guerra Alia: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, GlaxoSmithKline, MSD, PharmaMar, Roche Posay Company. J. Huang: Financial Interests, Personal and Institutional, Full or part-time Employment: Eisai Inc. J. McKenzie: Financial Interests, Personal and Institutional, Full or part-time Employment: Eisai Inc. G. Barresi: Financial Interests, Personal and Institutional, Full or part-time Employment: MSD Austria. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding accdemic trial: MSD, Clovis Oncology, PharmaMar; Financial Interests, Institutional, Funding, Grant for founding acamemic trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche; Non-Financial Interests, Member, Board of Directors: GCIG. All other authors have declared no conflicts of interest.

Background

Lymph node (LN) involvement is the key factor indicating adjuvant treatment in early-stage cervical cancer patients. Both macrometastases (MAC; >2mm) and micrometastases (MIC; 0.2-2 mm) are considered LN positive (pN1) since a negative impact of MIC similar to MAC has been confirmed by several studies. Although the majority of MIC are detected only by pathological ultrastaging of LN, no international protocol for pathological assessment has been agreed upon and still sparks controversy.

Methods

SENTIX is a prospective international observational study on sentinel lymph node (SLN) biopsy in cervical cancer patients conducted in 47 sites of 18 countries. Enrolled were patients with stage T1A1/L1 – T1B1 (<4 cm or ≤ 2 cm for fertility sparing; FIGO2018), common tumour types, no suspicious LN on imaging, and bilateral SLN detection. All detected SLN were intraoperatively examined by one section (standard assessment), and consequently processed by intensive protocol of pathological ultrastaging (2 mm slices embedded in paraffin; paraffin blocks sectioned completely in 150 μm intervals; two sections from each level, one stained with H&E and second examined immunohistochemically). Pathological SLN samples from randomly selected patients from each site were submitted for central quality assessment.

Results

Out of 647 prospectively enrolled patients, 82 were pN1 (12.7%), 43 with MAC and 39 with MIC (largest type of metastasis). Standard assessment detected only 56.1% of pN1 cases (83.7% MAC; 25.6% MIC) (Table). Additional 22 patients were diagnosed with isolated tumour cells (ITC; <0.2mm), 20 of them found by ultrastaging. Table: 526MO

SLN pathological assessment

Conclusions

The number of patients diagnosed with pN1 is directly related to the intensity of SLN pathological assessment. Pathological ultrastaging of SLN should be mandatory in patients with cervical cancer as it detects almost half of the cases with pN1. The protocol should consist of at least 4 levels.

Clinical trial identification

NCT02494063.

Legal entity responsible for the study

The authors.

Funding

Charles University in Prague (COOPERATIO) Ministry of Health of the Czech Republic (MH CZ – DRO-VFN64165) Czech Health Research Council (NV19-03-00023).

Disclosure

All authors have declared no conflicts of interest.

Background

In ATHENA–MONO (GOG-3020/ENGOT-ov45), progression-free survival (PFS) improvement was observed with first-line (1L) rucaparib maintenance treatment vs placebo in pts with advanced OC, regardless of molecular characteristics (median PFS, 20.2 vs 9.2 months, log-rank P<.0001; HR, 0.52; 95% CI, 0.40–0.68). Pts with or without high-risk clinical characteristics for disease progression were enrolled in ATHENA–MONO. In the subgroup analyses presented here, we sought to evaluate if all patients benefited from rucaparib 1L maintenance treatment, including those with more favourable prognostic factors at baseline.

Methods

Pts with high-grade, FIGO stage III–IV OC who had completed cytoreductive surgery and 4–8 cycles of 1L platinum-doublet chemotherapy with a response (partial [PR] or complete [CR]) were randomized 4:1 to oral rucaparib 600 mg BID or placebo. Investigator-assessed PFS was evaluated in pt subgroups based on FIGO stage, timing of surgery, and disease status post-chemotherapy.

Results

As of March 23, 2022 (data cutoff), 427 and 111 pts were randomized to rucaparib monotherapy vs placebo. The majority of patients had FIGO stage III disease (75%); approximately half underwent primary surgery (49%); and most patients had no residual disease post-chemotherapy (75%). In the intent-to-treat (ITT) population, investigator-assessed PFS was improved with rucaparib vs placebo across all subgroups based on FIGO stage, timing of surgery, and residual disease (Table). Table: 527MO

Conclusions

In the ITT population, 1L rucaparib maintenance treatment improved PFS vs placebo across subgroups regardless of timing of surgery or prognostic disease characteristics, including FIGO stage or residual disease. These results confirm a new maintenance treatment option for OC pts with or without high risk factors for progression at baseline irrespective of molecular characteristics.

Clinical trial identification

NCT03522246 May 11, 2018.

Editorial acknowledgement

Medical writing support and editorial support funded by Clovis Oncology, Inc. were provided by Sachi Yim and Frederique Evans of Ashfield MedComms, an Ashfield Health company.

Legal entity responsible for the study

Clovis Oncology, Inc.

Funding

Clovis Oncology, Inc.

Disclosure

R. Kristeleit: Financial Interests, Personal, Advisory Board: GSK, Eisai, Basilea Pharmaceutica, iTEOS, Clovis Oncology, Shattuck Labs, AstraZeneca, Regeneron; Financial Interests, Personal, Invited Speaker: GSK, Zydus Cadila, Clovis Oncology, AstraZeneca, GSK; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Personal, Other, Membert of Oncology and Haematology Expert Advisory Group: Commission on Human Medicines; Financial Interests, Institutional, Invited Speaker: GSK, Clovis Oncology, Clovis Oncology, Eisai, InCyte, AstraZeneca, MSD, Roche, BerGenBio, Allarity, IoVance, Artios, Regeneron; Financial Interests, Institutional, Research Grant: MSD. M. Lim: Financial Interests, Personal, Advisory Board: AstraZeneca, Boryung, GI Innovation, Takeda; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, CKD Pharm, Clovis Oncology, OncoQuest. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines: ESMO; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. J. Buscema: Financial Interests, Personal, Leadership Role: Arizona Oncology Associates; Financial Interests, Personal, Advisory Board: Caris Life Science; Financial Interests, Personal, Stocks/Shares: McKesson. P. Bessette: Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Canadian Cancer Trials Group, Clovis Oncology, Inc., Merck, Tesaro. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding accdemic trial: MSD, Clovis Oncology, PharmaMar; Financial Interests, Institutional, Funding, Grant for founding acamemic trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation receive: roche; Non-Financial Interests, Member, Board of Directors: GCIG. F. Marmé: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK/Tesaro, Clovis, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Roche, Gilead/immunomedics, Eisai, PharmaMar, GenomicHealth, Myriad, Seagen; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis, Roche, Eisai, Gilead/Immunomedics, MSD, German Breast Group, AGO Research GmbH, Vaccibody, GSK; Financial Interests, Institutional, Funding: AstraZeneca. T.J. Herzog: Financial Interests, Personal, Advisory Board: AstraZeneca, Caris, Clovis Oncology, Inc., Johnson & Johnson, Roche, Tesaro. I. McNeish: Financial Interests, Personal, Advisory Board, Advisory Boards: Clovis Oncology; Financial Interests, Personal, Advisory Board, Advisory Boards and travel: AstraZeneca, GSK; Financial Interests, Personal, Advisory Board: Roche, Alkermes, OncoC4, Theolytics; Financial Interests, Institutional, Funding: AstraZeneca; Non-Financial Interests, Invited Speaker, Trustee of this charity: Worldwide Cancer Research. S. Goble: Financial Interests, Personal, Stocks/Shares: Clovis Oncology; Financial Interests, Personal, Full or part-time Employment: Clovis Oncology. S. Hume: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. K. Fujiwara: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Takeda, Regenerone, Zeria; Financial Interests, Personal, Advisory Board: MSD, Eisai, Genmab, Nano Carrier, Daiichi Sankyo; Financial Interests, Institutional, Funding: Regenerone; Financial Interests, Institutional, Research Grant: MSD, Ono, Zeria, Genmab; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Leadership Role: GOTIC. B.J. Monk: Financial Interests, Personal, Advisory Role: Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Bayer, Clovis Oncology, Inc., Eisai, Genmab/Seattle Genetics, Elevar Therapeutics, EMD Merck, GOG Foundation, Gradalis, ImmunoGen, Iovance Biotherapeutics, Karyopharm Therapeutics, Merck, Mersana, Myriad Pharmaceuticals, Novocure, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Sorrento Therapeutics, Tesaro/GSK, US Oncology, Vascular Biogenics; Financial Interests, Personal, Leadership Role: US Oncology; Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Inc., Eisai, GSK, Merck, Roche/Genentech, Tesaro; Financial Interests, Other, Honoraria: Agenus, Akeso Biopharma, Aravive, AstraZeneca, Bayer, Clovis Oncology, Inc., Eisai, Elevar Therapeutics, EMD Merck, Genmab/Seattle Genetics, GOG Foundation, Gradalis, ImmunoGen, Lovance Biotherapeutics, Karyopharm Therapeutics, Macrogenics, Merck, Mersana, Myriad Pharmaceuticals, Novocure, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Sorrento Therapeutics, Tesaro/GSK, US Oncology, Vascular Biogenics; Financial Interests, Invited Speaker: Advaxis, Amgen, Array BioPharma, AstraZeneca, Genentech, Immunogen, Janssen, Lilly, Morphotek, Novartis, Nucana, Pfizer, Regeneron, Tesaro. All other authors have declared no conflicts of interest.

Background

PARP inhibitors (PARPi) have revolutionized the management of High-grade epithelial ovarian cancer (HGEOC) treatment. However, a significant number of patients relapse or progress under PARPi leading to the introduction of a new line of systemic therapy as chemotherapy. In patient with a limited number of metastatic sites in progression, -referred to as the oligo metastatic progression- a potential indication for local therapy followed by re introduction or continuation of PARPi treatment rather than initiating a new line of chemotherapy could be proposed. However, the impact of local treatment on progression free survival (PFS) in these patients remains unknown.

Methods

This international multicenter retrospective study evaluated the efficacy of PARPi continuation or reintroduction in patients with HGEOC after local treatment for oligometastatic progression. The main objective was to assess PFS under PARPi after local therapy (PFS post-LT). Secondary objectives included safety and OS.

Results

74 patients were identified in 20 centers between 04/20 and 11/21. 65% of patients were BRCA mutated and 92% had received ≥ 2 lines of prior systemic chemotherapy before the initial introduction of PARPi. Main progression sites were lymph nodes (42%), peritoneum (20%), liver (11%), other visceral (9%) and other (18%). Local therapy included radiotherapy (44%), surgery (43%), both (7%), cryotherapy or radiofrequency (3%) and other (3%). Median PFS post-LT was 11.5 months [95% CI 7.4; 17.2]. After median follow up of 14.8 months, 5 patients (6.8%) discontinued PARPi due to toxicity. The 1-year overall survival rate was 90.7% [95% CI 79.1; 96.0].

Conclusions

With close to one year without progression or introduction new line of systemic therapy, this study reports the feasibility and potential benefit of this original strategy in patients with oligometastatic progression under PARPi.

Legal entity responsible for the study

Centre Léon Bérard.

Funding

Has not received any funding.

Disclosure

M. Kfoury: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding accdemic trial: MSD, Clovis Oncology, PharmaMar; Financial Interests, Institutional, Funding, Grant for founding acamemic trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche; Non-Financial Interests, Member, Board of Directors: GCIG. A. Floquet: Financial Interests, Personal, Invited Speaker: AstraZeneca, Clovis Oncology, GSK, PharmaMar. L. Polastro: Financial Interests, Personal, Advisory Board: Advisory AstraZeneca. B. You: Financial Interests, Personal, Advisory Board: MSD, Astra-Zeneca, GSK-Tesaro, Bayer, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, Seagen, Myriad. T. De La Motte Rouge: Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, GSK, Clovis Oncology, Roche, Mylan, Tesaro; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Research Grant: Novartis, Pfizer, Msd, Seagen; Financial Interests, Institutional, Invited Speaker: Roche, Astrazeneca, Gsk, Msd, Pfizer, Netris Pharma; Non-Financial Interests, Advisory Role: French National Cancer Institute, Unicancer; Non-Financial Interests, Principal Investigator: ARCAGY. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1. All other authors have declared no conflicts of interest.

Background

The MEDIOLA (NCT02734004) study evaluated the efficacy and safety of olaparib+durvalumab (O+D doublet cohort) and O+D+bevacizumab (O+D+B triplet cohort) in patients (pts) with non-germline BRCA-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC). Previous efficacy data showed median progression-free survival (PFS) (95% CI) of 5.5 (3.6–7.5) and 14.7 (10.0–18.1) months (mo) with O+D and O+D+B, respectively (Drew et al, ESMO 2020). We now present the final analysis of overall survival (OS) and disease control rate (DCR) at 56 weeks (wks) in the O+D and O+D+B cohorts.

Methods

Pts had confirmed non-gBRCAm PSR OC and received 1–2 prior lines of platinum-based chemotherapy. Pts received O (300 mg bid) and D (1.5 g IV q4w), and B (10 mg/kg IV q2w; O+D+B cohort only) until disease progression. Survival follow-up took place at treatment discontinuation, monthly for 4 mo, and every 2–3 mo thereafter. OS and DCR at 56 wks were secondary endpoints.

Results

32 pts received O+D and 31 pts received O+D+B; 24/32 (75%) O+D and 20/31 (65%) O+D+B pts had received one prior line of chemotherapy. At data cutoff (17 Sep 2021), median follow-up for OS was 23.2 mo for O+D and 31.9 mo for O+D+B. Kaplan–Meier estimates of median OS (95% CI) were 26.1 (18.7–not calculable [NC]) mo for O+D and 31.9 (22.1–NC) mo for O+D+B. Probabilities of survival (95% CI) in the O+D and O+D+B cohorts, respectively, were 77.6 (58.6–88.6) and 96.8 (79.2–99.5) at 12 mo and 50.8 (32.1–66.8) and 64.5 (45.2–78.5) at 24 mo. DCR at 56 wks (90% CI) was 9.4% (2.6–22.5) for O+D and 38.7% (24.1–55.0) for O+D+B. Safety data are shown in the Table. Table: 529MO

Conclusions

Based on the reported final OS and DCR at 56 wks data, treatment with O+D+B demonstrated promising efficacy in pts with non-gBRCAm PSR OC. O+D and O+D+B safety profiles were consistent with that expected for the single agents; no new safety signals emerged with longer follow-up.

Clinical trial identification

NCT02734004.

Editorial acknowledgement

Medical writing assistance was provided by Caroline Wadsworth, PhD, at Cence, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S. Banerjee: Financial Interests, Institutional, Research Grant: AstraZeneca and GlaxoSmithKline; Financial Interests, Personal, Other, Consulting: Amgen, AstraZeneca, Genmabs, GlaxoSmithKline, Immunogen, Merck Sharpe & Dohme, Merck Sereno, and Shattuck Labs; Financial Interests, Personal, Other, Personal fees: Amgen, AstraZeneca, Clovis Oncology , Merck Sharpe & Dohme, Mersana, Pfizer, and Roche; Non-Financial Interests, Personal, Other, Unpaid participation: Epsilogen; Non-Financial Interests, Personal, Other, Unpaid role as Director of Membership: European Society of Medical Oncology. M. Imbimbo: Financial Interests, Personal, Advisory Role: Immatics. P. Roxburgh: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: AstraZeneca and Tesaro. J. Kim: Financial Interests, Personal, Advisory Role: Takeda Korea, GSK Korea, Boryung, Vifor Pharma, MSD Korea; CMIC Korea, AstraZeneca, Janssen, LG Pharma . M.H. Kim: Financial Interests, Personal, Research Grant: AstraZeneca. R. Plummer: Financial Interests, Personal, Other, Personal fees: Pierre Faber, Bayer, Novartis, BMS, Cybrexa, Ellipses, CV6 Therapeutics, Immunocore, Genmab, Astex Therapeutics, Medivir, Onxeo, Alligator Biosciences, GSK, SOTIO Biotech AG and Sanofi Aventis. S. Stemmer: Financial Interests, Institutional, Research Grant: CAN-FITE, AstraZeneca, Bioline RX, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelexis, Geicam, MSD, AbbVie, Tayga biopharmaceutics, Halozyme, Incyte, Lilly, Moderna, Teva pharmaceuticals, Roche; Financial Interests, Personal, Stock/Shares: CTG Pharma, DocBoxMD, Tyrnovo, VYPE, Cytora, Remiwise, CAN-FITE. B. You: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Clovis, ECS Progastrin, GlaxoSmithKline, Merck Sharp & Dohme, Novartis and Roche; Financial Interests, Personal, Other, Travel support: AstraZeneca, Bayer Merck Sharp & Dohme and Roche. R.T. Penson: Financial Interests, Personal, Funding: Array BioPharma Inc., AstraZeneca, Eisai Inc., Genentech, Inc., Regeneron, Sanofi-Aventis US LLC, Tesaro Inc., Vascular Biogenics Ltd; Financial Interests, Personal, Royalties: BMJ Publishing, Elsevier, UptoDate, Wolters Kluwer Health, Wiley Blackwell; Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, Cancer Panels, Care4ward (unpaid), Eisai, Genentech, GlaxoSmithKline, Merck & Co., Roche Pharma, Sutro Biopharma, Vascular Biogenics, WebMD. D. O'Malley: Financial Interests, Personal, Funding: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc, Cerulean Pharma, GOGFoundation, Bristol-Myers Sq; Financial Interests, Personal, Advisory Role: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche Ambry, GOGFoundation, Iovance, Myriad Genetics, Eisai, Agenus, Tarveda, Merck, SeaGen, Novartis, Mersana, Clovis, Rubis, Elevar, Takeda, Toray, INXMED, S. K. Meyer: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. H. Gao: Financial Interests, Personal, Full or part-time Employment, employment or stock ownership with AstraZeneca: AstraZeneca; Financial Interests, Personal, Stocks/Shares, employment or stock ownership with AstraZeneca: AstraZeneca. H. Angell: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Tablante Nunes: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Domchek: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb and Clovis. Y. Drew: Financial Interests, Personal, Advisory Role: AstraZeneca, Clovis Oncology, Genmab, Merck and Tesaro; Financial Interests, Institutional, Funding: AstraZeneca, Clovis Oncology, Genmab, Merck and Tesaro; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Clovis Oncology, Genmab, Merck and Tesaro. All other authors have declared no conflicts of interest.