Search

Aim: To understand the impact of the niraparib individualized starting dose (ISD), compared with fixed starting dose (FSD), on the cost of hematologic adverse event (AE) management from a US payer perspective. Methods: The frequencies of grade ≥3 hematologic AEs that occurred in >1% of patients treated with niraparib were obtained from the primary analysis results of the phase III PRIMA/ENGOT-OV26/GOG-3012 trial. US unit costs for each grade ≥3 AE in the base case were obtained from the 2017 Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project database; unit costs were adjusted to 2020 US dollars. AE management costs per patient were calculated by multiplying AE unit cost by the frequency of each AE by niraparib starting dose. Because AEs were assumed to occur independently of one another, costs were added to derive the total cost. Results: For niraparib, the estimated AE management cost per patient was lower for the ISD than the FSD for all hematologic AEs (FSD vs ISD: thrombocytopenia, $4701.87 vs $1921.89; anemia, $2784.00 vs $1760.59; platelet count decreased, $2103.47 vs $922.51; neutropenia, $2112.50 vs $1369.56; neutrophil count decreased, $1285.87 vs $770.38). The total mean calculated AE management cost per patient was $12,987.71 with the FSD and $6744.93 with the ISD. Conclusion: For niraparib, the cost of managing hematologic AEs in the US was reduced by almost half with the ISD compared with the FSD. The cost reduction and improvements in safety associated with the niraparib ISD support its use in clinical practice.

Objective: To evaluate the impact of age on the efficacy and safety of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first-line platinum-based chemotherapy., Methods: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016). Patients in the intent-to-treat population were categorized according to age at baseline (<65 years vs ≥65 years), and progression-free survival (PFS), safety, and health-related quality of life (HRQOL) were evaluated for each age subgroup (clinical cutoff date, May 17, 2019). Safety findings were also evaluated according to a fixed starting dose (FSD) or an individualized starting dose (ISD)., Results: Of 733 randomized patients, 289 (39.4%) were ≥65 years (190 niraparib, 99 placebo) at baseline. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) were similar in patients aged <65 years (13.9 vs 8.2 months; HR, 0.61 [0.47-0.81]) and ≥65 years (13.7 vs 8.1 months; HR, 0.53 [0.39-0.74]). The incidences of any-grade and grade ≥3 treatment-emergent adverse events (TEAEs) were similar across age subgroups; in the niraparib arm, TEAEs leading to dose discontinuation occurred in 7.8% of patients <65 years and 18.4% of patients ≥65 years. ISD use lowered the incidence of grade ≥3 thrombocytopenia events in niraparib-treated patients compared with the FSD (<65 years: 42.8% vs 18.0%; ≥65 years 57.0% vs 26.1%). HRQOL was comparable across age subgroups., Conclusion: Niraparib efficacy, safety, and HRQOL were generally comparable across age subgroups, although patients ≥65 years had a higher rate of discontinuations due to TEAEs. ISD use reduced grade ≥3 thrombocytopenia events regardless of age., Competing Interests: Declaration of competing interest Dr. Valabrega reports consulting fees from GSK; honoraria from AstraZeneca, Eisai, GSK, and MSD; travel support from AstraZeneca and PharmaMar; and participation in advisory boards for AstraZeneca, Eisai, GSK, and MSD. Dr. Pothuri reports institutional grant support from AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, GSK, I-Mab, Immunogen, Incyte, Karyopharm, Merck, Mersana, Onconova, SeaGen, Sutro, and Toray; consulting fees from AstraZeneca, GOG Foundation, GSK, Merck, and Seagen; support for attending meetings from GOG Partners; and advisory board fees from Arquer Diagnostics, Atossa, Deciphera, Eisai, Elevar Therapeutics, GOG Foundation, I-Mab, Immunogen, Lily, Merck, Mersana, Natera, Onconova, Regeneron, Sutro Biopharma, Tesaro/GSK, Toray, and VBL Therapeutics. Dr. Oaknin reports institutional grants from AbbVie Deutschland, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics AB, BMS, Clovis Oncology, Eisai, F. Hoffmann–La Roche, Immunogen, MSD de España SA, Millennium Pharmaceuticals, PharmaMar SA, Regeneron Pharmaceuticals, and Tesaro; consulting fees from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, Exelixis, EMD Serono, F. Hoffmann–La Roche, Genmab, GSK, ImmunoGen, Iteos, MSD de España SA, Mersana Therapeutics, Novocure, OncXerna Therapeutics, PharmaMar, Regeneron, Shattuck Labs, Seagen, and Sutro Biopharma; honoraria from Asociación Colombiada de Ginecológos Oncólogos, AstraZeneca, ESO, GSK, Medscape, NSGO, Peerview, and Peervoice; individual travel support from AstraZeneca, PharmaMar, and Roche; and advisory board participation for Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, Exelixis, EMD Serono, F. Hoffmann–La Roche, Genmab, GSK, ImmunoGen, Iteos, MSD de España SA, Mersana Therapeutics, Novocure, OncXerna Therapeutics, PharmaMar, Regeneron, Seagen, Shattuck Labs, and Sutro Biopharma. Dr. Graybill reports consulting and speaker fees from GSK. Dr. Sánchez reports consulting fees from AstraZeneca, GSK, and MSD; honoraria from AstraZeneca, GSK, and MSD; and travel support from AstraZeneca, GSK, and MSD. Dr. McCormick reports personal fees for advisory boards for Clovis, GSK, ImmunoGen, and Merck. Dr. Baurain reports consulting fees from AstraZeneca, BMS, GSK, Immunocore, Merck, MSD, Novartis, Pfizer, Pierre-Fabre, Regeneron, Sanofi, and Sun Pharma. Dr. Tinker reports honoraria from AstraZeneca, Eisai, GSK, and Merck and travel support from GSK. Dr. Denys reports an institutional research grant from Gilead; consulting fees from Gilead and GSK; honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, GSK, Leo Pharma, MSD, and Roche; travel support from AstraZeneca, Gilead, GSK, MSD, Pfizer, PharmaMar, Roche, and Teva; and participation on advisory boards for AstraZeneca, Eli Lilly, Gilead, GSK, Menarini, MSD, and Pfizer. Dr. O'Cearbhaill reports institutional research support from NIH/NCI Cancer Center Support Grant (P30 CA008748) and support grants from AstraZeneca/Merck, Atara Biotherapeutics/Bayer, Genentech, Genmab, GSK, Gynecologic Oncology Group Foundation, Juno Therapeutics, Kite/Gilead, Ludwig Institute for Cancer Research, Regeneron, Sellas Life Sciences, StemcentRx, Syndax, TapImmune, and TCR2 Therapeutics; participating in advisory boards with Bayer, Carina Biotech, Fresenius Kabi, Immunogen, Regeneron, R-Pharm, Seattle Genetics, and Tesaro/GSK; personal fees from GOG Foundation; travel fees from Hitech Health; and service as a noncompensated steering committee member for the DUO-O (olaparib) and PRIMA and Moonstone (niraparib) studies. Dr. Hietanen reports consulting fees from AstraZeneca, Eisai, GSK, and MSD and honoraria from AstraZeneca and GSK. Dr. Moore reports institutional grants from Angle Plc and Fujirebio Diagnostics and personal fees from Fujirebio Diagnostics. Dr. Knudsen has nothing to disclose. Dr. de La Motte Rouge reports receiving consulting fees from AstraZeneca, Clovis Oncology, Eisai, Gilead, GSK, MSD, Novartis, Pfizer, and Sanofi; receiving honoraria from AstraZeneca, GSK, MSD, NetCancer, and Pfizer; and travel support from Gilead, MSD, and Pfizer. Dr. Heitz reports honoraria from AstraZeneca, GSK, Roche, and Tesaro and consulting fees from AstraZeneca, GSK, Roche, and Tesaro. Dr. Levy has nothing to disclose. Dr. Monk reports consulting fees from Agenus, Akeso Biopharma, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, MacroGenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, and VBL and speakers' bureau honoraria from AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech, and Tesaro/GSK. Dr. González-Martín reports for different educational or advisory-related activities from Alkermes, Amgen, AstraZeneca, Clovis, Genmab, GSK, Hedera Dx, Immunogen, Illumina, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Roche, Seagen, Sotio, Sutro, Takeda, and Tubulis. Ms. York is a current employee of GSK. Dr. Gupta is a former employee of GSK and Mersana Therapeutics and is currently an employee of Cullinan Oncology., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To identify characteristics associated with long-term progression-free survival (≥2 years) in patients with advanced ovarian cancer treated with niraparib first-line maintenance therapy in the phase III PRIMA/ENGOT-OV26/GOG-3012 study., Methods: In this post hoc analysis of PRIMA, patients randomized to niraparib were grouped based on investigator-assessed progression-free survival (progressive disease/censoring <2 years or ≥2 years after randomization). Variables assessed for predictive value were Eastern Cooperative Oncology Group performance status, International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis, clinical response to platinum-based chemotherapy, number of prior chemotherapy cycles, primary tumor location, body mass index, categorical age, debulking surgery type, number of baseline target lesions, number of baseline non-target lesions, BRCA /homologous recombination-deficiency status, residual disease status, and duration from end of chemotherapy to randomization. Logistic regression modeling using backward elimination (significance level=0.15) identified covariates associated with long-term progression-free survival (clinical cut-off date November 17, 2021)., Results: Of 487 patients randomized to niraparib, 152 (31%) had progressive disease/censoring ≥2 years after randomization. Multivariable logistic regression modeling using backward elimination identified BRCA1/2 mutation/homologous recombination deficiency status (p<0.0001), FIGO stage (p=0.041), primary tumor location (p=0.095), and number of baseline non-target lesions (p=0.0001) to be associated with long-term progression-free survival. Patients significantly more likely to achieve progression-free survival of ≥2 years in the final model were those with BRCA1 - and BRCA2 -mutated/homologous recombination-deficient tumors or BRCA wild-type/not determined/homologous recombination-deficient tumors (vs BRCA wild-type/homologous recombination-proficient/not determined tumors), FIGO stage III (vs IV), and 0 or 1 baseline non-target lesions (vs ≥2 baseline non-target lesions)., Conclusions: The hypothesis-generating results of this analysis suggest that BRCA1/2 mutation/homologous recombination-deficiency status, FIGO stage, and number of baseline non-target lesions may predict progression-free survival of ≥2 years in patients with advanced ovarian cancer receiving niraparib first-line maintenance therapy., Trial Registration Number: NCT02655016., Competing Interests: Competing interests: WSG reports consulting and speaker fees from GSK. BPB reports honoraria, support for attending meetings and/or travel from AstraZeneca, Clovis, GSK, MSD, and PharmaMar and advisory board fees from AstraZeneca, Clovis, GSK, and MSD. DMO reports personal fees (consulting and/or advisory boards) and funding for clinical research from AbbVie, Amgen, AstraZeneca, Clovis, Eisai, Genentech/Roche, GOG Foundation, Immunogen, Iovance, Janssen/J&J, Merck, Mersana, Novocure, Regeneron, SDP Oncology (BBI), Seagen, and Tesaro/GSK; funding for clinical research from Ajinomoto, Array Biopharma, Bristol-Myers Squibb, Cerulean Pharma, EMD Serono, Ergomed, Genmab, INC Research, inVentiv Health Clinical, Ludwig Cancer Research, New Mexico Cancer Care Alliance, PRA Intl, Serono, Stemcentrx, TRACON Pharmaceuticals, VentiRx, and Yale University; personal fees from Myriad Genetics, Rubis, and Tarveda; personal fees and funding for clinical research from Agenus; and personal fees (consulting and/or advisory boards) from Ambry, Arquer Diagnostics, Celsion, Corcept Therapeutics, Elevar, InxMed, Novartis, Roche Diagnostics MSA, Sorrento, Takeda, and Toray. IV reports institutional payments for corporate-sponsored research from Amgen and Roche and contracted research from Genmab and Oncoinvent AS; institutional consulting fee payments from Amgen (Europe) GmbH, AstraZeneca, Carrick Therapeutics, Clovis Oncology, Deciphera Pharmaceuticals, Elevar Therapeutics, F. Hoffmann–La Roche, Genmab, GSK, Immunogen, Mersana, Millennium Pharmaceuticals, MSD, Novocure, Octimet Oncology, Oncoinvent AS, Sotio AS, Verastem Oncology, and Zentalis; consulting fees from Deciphera Pharmaceuticals, Jazz Pharma, and Oncoinvent AS; honoraria payment from Agenus, Aksebio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, F. Hoffmann–La Roche, Genmab, GSK, Immunogen, Jazz Pharma, Karyopharm, MSD, Novartis, Novocure, Oncoinvent AS, Seagen, and Sotio AS; institutional travel support from Amgen, AstraZeneca, MSD, Roche, and Tesaro; and advisory board fees from Agenus, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals (2021), Eisai, F. Hoffmann–La Roche, Genmab, GSK, Immunogen, MSD, Novartis, Novocure, Seagen (2021), and Sotio AS. BJM reports consulting fees from Agenus, Akeso Bio, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, MacroGenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, VBL, and speakers’ bureau honoraria from AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech, and Tesaro/GSK. AA reports advisory board fees from GSK and MSD. LJC reports institutional research funding from AbbVie, Advaxis, Agenus, Ajinomoto, Arcus Biosciences, Array BioPharma, AstraZeneca, BeiGene USA, BMS, Cerulean Pharma, Clovis Oncology, Deciphera Pharma, Eisai, EMD Serono, Ergomed Clinical Research, Exelixis, Genentech/Roche, Genmab, GSK, Hoffman–LaRoche, Immunogen, Incyte Corporation, Iovance Biotherapeutics, InVentiv Health Clinical, Jansen R&D, Karyopharm, Leap Therapeutics, Ludwig Institute of Pharmaceuticals, Merck, Mersana Therapeutics, Novocure, OncoQuest, OvaGene, Pfizer, PharmaMar, PRA International, Precision Therapeutics, Regeneron, Sanofi, Seattle Genetics, Serono, Stemcentrx, Sumitomo Dainippon Pharma Oncology, Sutro Biopharma, Tesaro (GSK), TRACON Pharm, and Verastem; personal advisory board fees from A28 Therapeutics, Celsion Corporation, Corcept Therapeutics, Elevar Therapeutics, GSK, Immunogen, InxMed, Luzsana Biotechnology, Myriad Genetics, Onconova, Rubius Therapeutics, Sorrento Therapeutics, Toray Industries, and VBL Therapeutics; and member of the data monitoring committee for Corcept Therapeutics. RS reports support for attending meetings from MSD and advisory board fees from Clovis Oncology, GSK, and MSD. TJH reports personal consulting fees from Aadi, AstraZeneca, Caris, Clovis, Eisai, Epsilogen, Genelux, Genentech, GSK, Immunogen, J&J, Merck, Mersana, and Seagen; participation on a data safety monitoring board or advisory board for Corcept; and leadership role on the GOG Foundation Board and president of GOG Partners. PF reports payment or honoraria and payment for expert testimony from AstraZeneca, Clovis, Daiichi, GSK, and Novartis and support for attending meetings from AstraZeneca, Daiichi, GSK, and Novartis. BP reports institutional grant support from AstraZeneca, Celsion, Clovis Oncology, Duality Bio, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Seagen, Sutro Biopharma, Takeda Pharmaceuticals, Tesaro/GSK, Toray, and VBL Therapeutics; consulting fees from AstraZeneca, BioNtech, Clovis Oncology, Eisai, GOG Foundation, Lily, Merck, Mersana, Seagen, Sutro Biopharma, Tesaro/GSK, Onconova, and Toray; and travel support from GSK and BioNtech. EIB reports honoraria from AstraZeneca, GSK, and Merck; consulting or advisory roles at AstraZeneca and GSK; institutional research funding from AstraZeneca, Bayer, Clovis, Eisai, GSK, Merck, and Resolve; travel support from AstraZeneca; and relationship with medical director of the North Eastern German Society of Gynecological Oncology (NOGGO). CM reports advisory role fees from AstraZeneca, Clovis, GSK, ImmunoGen, and Merck. AY reports a GEICO grant by GSK. RGM reports personal fees from Fujirebio Diagnostics and research funding from Angle plc. PV reports payment of honoraria to self from MSD, Novartis, and Roche. NR-J reports advisory board fees from Eisai. WY and JH are employees of GSK. AG-M reports fees for different educational or advisory-related activities from Alkermes, Amgen, AstraZeneca, Clovis, Eisai, Genmab, GSK, Hedera Dx, Immunogen, Illumina, Karyopharm, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Regeneron, Roche, Seagen, Sotio, Sutro, Takeda, and Tubulis., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objective: Progression-free survival is an established clinically meaningful endpoint in ovarian cancer trials, but it may be susceptible to bias; therefore, blinded independent centralized radiological review is often included in trial designs. We compared blinded independent centralized review and investigator-assessed progressive disease performance in the PRIMA/ENGOT-ov26/GOG-3012 trial examining niraparib monotherapy., Methods: PRIMA/ENGOT-ov26/GOG-3012 was a randomized, double-blind phase 3 trial; patients with newly diagnosed stage III/IV ovarian cancer received niraparib or placebo. The primary endpoint was progression-free survival (per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), determined by two independent radiologists, an arbiter if required, and by blinded central clinician review. Discordance rates between blinded independent centralized review and investigator assessment of progressive disease and non-progressive disease were routinely assessed. To optimize disease assessment, a training intervention was developed for blinded independent centralized radiological reviewers, and RECIST refresher training was provided for investigators. Discordance rates were determined post-intervention., Results: There was a 39% discordance rate between blinded independent centralized review and investigator-assessed progressive disease/non-progressive disease in an initial patient subset (n=80); peritoneal carcinomatosis was the most common source of discordance. All reviewers underwent training, and as a result, changes were implemented, including removal of two original reviewers and identification of 10 best practices for reading imaging data. Post-hoc analysis indicated final discordance rates between blinded independent centralized review and investigator improved to 12% in the overall population. Median progression-free survival and hazard ratios were similar between blinded independent centralized review and investigators in the overall population and across subgroups., Conclusion: PRIMA/ENGOT-ov26/GOG-3012 highlights the need to optimize blinded independent centralized review and investigator concordance using early, specialized, ovarian-cancer-specific radiology training to maximize validity of outcome data., Competing Interests: Competing interests: TJH has served on advisory boards (Aravive, AstraZeneca, Caris, Clovis Oncology, Eisai, Epsilogen, GSK, Immunogen, Johnson & Johnson, Merck, Roche Genentech, Seagen) and as a consultant for Abbvie. SAW reports consulting fees (GSK and BioClinica). MRM reports personal fees and other (Karyopharm Therapeutics, Sera Prognostics, Roche); institutional grants and no financial interest (Apexigen, AstraZeneca, Deciphera, GSK, Ultimovacs); personal fees and invited speaker (AstraZeneca, GSK); personal fees and advisory boards (AstraZeneca, Biocad, Boehringer Ingelheim, GSK, Karyopharm, Merck, Mersana, ImmunoGen, Clovis Oncology, Roche, Zailab); personal fees, stocks and a member of board of directors (Karyopharm). BP reports research funding (AstraZeneca, Celgene, Celsion, Clovis, Genentech, SeaGen, GSK, Merck, Mersana, SeaGen, Takada, Toray) and consulting fees (AstraZeneca, Celsion, Eisai, GSK, GOG Foundation, Immunogen, Inxmed, Lily, Merck, Mersana, SeaGen, Toray). IV reports consulting fees (Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Exelixis, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncoXerna, Regeneron, Sanofi, Seagen, Sotio, Verastem Oncology, Zentalis), travel grants (Karyopharm, Genmab, Novocure), and contracted research grants (Amgen, Roche, Oncoinvent AS). WSG reports advisory board and speaker fees (GSK). IAM, WY, and DG are employees of GSK. JAH is an employee of GSK and reports stocks in GSK. AGM reports personal fees for educational/advisory-related activities (Alkermes, Amgen, AstraZeneca, Clovis, Genmab, GSK, Immunogen, Mersana, MSD, Novocure, Oncoinvent, PharmaMar, Roche, SOTIO, Takeda). BJM reports consulting fees (Acrivon, Adaptimmune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Eisai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyoparm, Iovance, Laekna, Macrogenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, GSK, US Oncology Research, VBL, Verstem, Zentalis); speakers honoraria (AstraZeneca, Clovis, Eisai, Merck, Myriad, Roche/Genentech, GSK); investigator honoraria (Gradalis)., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction., Methods: S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450., Findings: From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group)., Interpretation: In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction., Funding: Agency for Healthcare Research and Quality and the National Cancer Institute., Translation: For the Spanish translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests GLA received payments to Fred Hutch for support for the present manuscript. AAS has grants or contracts from AbbVie, Aravive, AstraZeneca, Boehringer, Ingelheim, Clovis, Eisai, Ellipses, Immunogen, Merck, Oncoquest, Roche/Genentech, SeagenInc, TapImmune, Tesaro/GSK, VBL Therapeutics, and National Cancer Trial Network; has received honoraria for educational presentations or lectures from @Point of Care, Clinical Care Optios, Curio Science, Peerview, Bio ASCEND, RTP, and GOG Foundation; has received honorarium from Myriad; and has received support for attending meetings or travel from GOG, Society of Gynecologic Oncology, and NRG. DCF received support for the present manuscript in the form of payments through S1316 to Valley Health for patient enrolment; received payment or honoraria for lectures from Intuitive for the resident lecture programme; and has stock options in Intuitive. JDW has grants or contracts from Merck; receives royalties or licenses from UptoDate; receives payments for expert testimony from Medicolegal for consulting on gynaecological cancer; is a journal editor for the American College of Obstetricians and Gynecologists. BFa received visiting professor honoraria in April, 2022, at the Ohio State University Department of Surgery, October, 2021, at the University of Nebraska Department of Surgery, and December, 2020, at the University of Tennessee Department of Surgery; and has stock or stock options in Align Tech, Biogen, Bristol Myers Squibb, DexCom, Editas Medicine, Fulgent Genetics, GoodRx Holdings, Guardant Health, Globus Medical, Healthequity, HCA Healthcare, IDEXX Laboratories, Illumina, Intuitive Surgical, Invitae, Masimo, Moderna, Neurocrine Bioscience, Novocure, Quidel, Repligen, Seagen, Shockwave Medical, STAAR Surgical, UnitedHealth Group, Veeva Systems, Teladoc Health, and ResMed. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trial was amended to prospectively evaluate the safety and efficacy of an individualized starting dose (ISD) regimen of niraparib for first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer., Methods: In the phase 3 PRIMA trial, patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first-line platinum-based chemotherapy (N = 733) were initially treated with a fixed starting dose (FSD) regimen of 300 mg once daily. Subsequently, the protocol was amended so newly enrolled patients received an ISD: 200 mg once daily in patients with baseline body weight < 77 kg or baseline platelet count < 150,000/µL, and 300 mg once daily in all other patients. Efficacy and safety outcomes were assessed by starting dose., Results: Overall, 475 (64.8%) patients were assigned to an FSD (niraparib, n = 317; placebo, n = 158) and 258 (35.2%) were assigned to an ISD (niraparib, n = 170; placebo, n = 88). Efficacy in patients who received FSD or ISD was similar for the overall (FSD hazard ratio [HR], 0.59 [95% CI, 0.46-0.76] vs. ISD HR, 0.69 [95% CI, 0.48-0.98]) and the homologous recombination-deficient (FSD HR, 0.44 [95% CI, 0.30-0.64] vs. ISD HR, 0.39 [95% CI, 0.22-0.72]) populations. In patients with low body weight/platelet count, rates of grades ≥3 and 4 hematologic treatment-emergent adverse events, dose interruptions, and dose reductions were lower for those who received ISD than for those who received FSD., Conclusions: In PRIMA, similar dose intensity, similar efficacy, and improved safety were observed with the ISD compared with the FSD regimen., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)