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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.

Objectives: Real-world data evaluating how approvals of novel treatment regimens for ovarian cancer have impacted the treatment paradigm, including first-line maintenance, are lacking. This analysis aimed to describe treatment patterns for advanced epithelial ovarian cancer in Europe and the USA in the first-line maintenance setting. Patient characteristics, biomarker testing rates, and drivers of treatment choice were also evaluated., Methods: A retrospective chart review study of electronic medical records in Europe and the USA was conducted for patients diagnosed with epithelial ovarian cancer (June 1, 2017-May 31, 2020), in line with Healthcare Market Research guidelines. Eligible physicians extracted data from electronic medical records by completing standardized patient record forms, including questions on patient involvement in treatment decisions. Patients with advanced (stage III/IV) disease were stratified by country and diagnosis date to provide information on treatment patterns., Results: Patient record forms for 7072 patients with epithelial ovarian cancer were completed by 416 physicians; 5386 patients had stage III/IV ovarian cancer. Over time, the percentage of patients who were tested for BRCA mutations or homologous recombination deficiency increased. Patient preference was documented as a reason for treatment selection in approximately one-sixth of cases in the first-line adjuvant and first-line maintenance settings. The use of first-line maintenance poly(ADP-ribose) polymerase inhibitor monotherapy increased over time, while the use of vascular endothelial growth factor inhibitor monotherapy decreased., Conclusions: This real-world study showed that treatment patterns for advanced epithelial ovarian cancer varied by country. Rates of physician-reported patient involvement in treatment decisions in the first-line adjuvant and maintenance treatment settings for ovarian cancer were low, highlighting an unmet need for initiatives to improve patient involvement in shared decision-making regarding maintenance therapy selection., Competing Interests: Competing interests: The authors disclose the following potential conflicts of interest: KNM: Institutional research grant: Angle PLC; Consulting fees: Fujirebio Diagnostics Inc; Advisory fees: GSK. MRM: Advisory board fees: Allarity Therapeutics, AstraZeneca, Biocad, BioNTech, Boehringer Ingelheim, Clovis, Daiichi-Sankyo, Eisai, Genmab, GSK, ImmunoGen, Incyte, Karyopharm, Merck/MSD, Mersana, Novartis, Regeneron, Roche, Seagen, Takeda, Tesaro, Zailab; membership on the board of directors or stockholder/shareholder: Karyopharm Therapeutics, Sera Prognostics; Institutional research grants: Allarity, Apexigen, AstraZeneca, Boehringer Ingelheim, Clovis, GSK, Novartis, Tesaro, Ultimovacs; Trial chair: AstraZeneca, Boehringer Ingelheim, Deciphera, Daiichi-Sankyo, GSK, Merck, Mersana, NuvationBio, Tesaro. SP: Honoraria: AstraZeneca, GSK, MSD, Roche; Research funding: AstraZeneca, GSK, MSD, Pfizer, Roche. CG: Honoraria/consultancy fees: AstraZeneca, Chugai, Clovis, Cor2Ed, Eisai, GSK, MSD, Peer Voice, Takeda; Research funding: Aprea, Artios, AstraZeneca, BerGen Bio, GSK, Medannexin, MSD, Novartis, NuCana; Issued/pending patents related to predicting treatment response in ovarian cancer. DL: Grants or contracts: Alkermes, AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, ImmunoGen, Incyte, MSD, Novartis, Pharma&, Pharmamar, Roche, Seagen; Consulting fees: AstraZeneca, Clovis Oncology, Corcept, Daiichi Sankyo, Genmab, GSK, ImmunoGen, MSD, Novartis, Novocure, Oncoinvest, Seagen, Sutro; Honoraria: AstraZeneca, Corcept, Genmab, GSK, ImmunoGen, MSD, Seagen; Support for attending meetings and/or travel: AstraZeneca, GSK, Menarini, MSD; Participation on a data safety monitoring board or advisory board: AstraZeneca, Clovis Oncology, Corcept, Daiichi Sankyo, Genmab, GSK, ImmunoGen, MSD, Novocure, Oncoinvest, Seagen, Sutro; Leadership or fiduciary roles: ENGOT, GCIG, MITO. BJM: Consulting fees: Acrivon, Adaptimune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Eisai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Iovance, Karyopharm, Laekna, MacroGenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, Teasro/GSK, US Oncology Research, VBL, Verastem, Zentalis; Speakers’ bureau honoraria: AstraZeneca, Eisai, Myriad, Roche/Genentech, Tesaro/GSK. JS: Grants or contracts: GSK, Roche; Consulting fees: Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Merck Sharp & Dohme, MSD, Novartis, Oncoinvent, Pfizer/Merck, PharmaMar, Roche; Honoraria fees: AstraZeneca, Clovis, Eisai, MSD, PharmaMar, Roche, Tesaro/GSK; Support for attending meetings: AstraZeneca, PharmaMar, Roche, Tesaro/GSK. JMS: Employee of GSK. ND'E: Employee of Genactis (the company that was contracted to perform the statistical analyses). AG-M: Fees for different educational or advisory-related activities: Alkermes, Amgen, AstraZeneca, Clovis, Eisai, Genmab, GSK, Hedera Dx, Immunogen, Illumina, Karyopharm, Macrogenics, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Regeneron, Roche, Seagen, Sotio, Sutro, Takeda, Tubulis., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

The clinical development of antibody drug conjugates (ADCs) in ovarian cancer began in 2008 with farletuzumab, a humanized monoclonal antibody, and vintafolide, an antigen drug conjugate, both targeting alpha folate receptor. Over the years, this novel class of drugs expanded to agents with a more sophisticated design and structure, targeting tissue factor (TF) in cervical cancer or human epidermal growth factor receptor 2 (HER2) in endometrial cancer. Despite the impressive number of patients included in clinical trials investigating different ADCs across gynecological cancers, it was only recently that the Food and Drug Administration (FDA) granted accelerated approvals to the first ADCs in gynecologic cancer. In September 2021, the FDA approved tisotumab vedotin (TV) in recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. This was followed in November 2022, by the approval of mirvetuximab soravtansine (MIRV) for adult patients with folate receptor alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Currently, the field of ADCs is rapidly expanding and more than 20 ADC formulations are in clinical trials for the treatment of ovarian, cervical and endometrial tumors. This review summarizes key evidence supporting their use and therapeutic indications, including results from late-stage development trials investigating MIRV in ovarian cancer and TV in cervical cancer. We also outline new concepts in the field of ADCs, including promising targets such as NaPi2 and novel drug delivery platforms such as dolaflexin with a scaffold-linker. Finally, we briefly present challenges in the clinical management of ADC toxicities and the emerging role of ADC combination therapies, including chemotherapy, anti-angiogenic and immunotherapeutic agents., Competing Interests: Competing interests: SM: Research funding, advisory board, honorary or travel expenses: AbbVie, AstraZeneca, Clovis, Eisai, GlaxoSmithKline, Hubro, Medac, MSD, Novartis, Nykode, Olympus, PharmaMar, Pfizer, Roche, Sensor Kinesis, Teva, Tesaro. DL: Research funding: Clovis Oncology, AstraZeneca, Corcept Therapeutics, GlaxoSmithKline, Genmab, ImmunoGen, Merck Sharp & Dohme, Novartis, PharmaMar, Roche, and Seagen; Consulting fees: Clovis Oncology, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and PharmaMar; Payment or honoraria for lectures: Clovis Oncology, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, and Seagen; Support for attending meetings and/or travel: AstraZeneca, PharmaMar, and Roche; Participation on a data safety monitoring board or advisory board: Clovis Oncology, Agenus, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and Roche; and serves on the board of directors for GCIG and as chair of GCA for ENGOT. KNM: Leadership: GOG Partners, NRG Oncology (Inst); Honoraria: Research To Practice, Prime Oncology, Physicans’ Education, Resource, Great Debates and Updates; Consulting or Advisory Role: Genentech/Roche, Immunogen, AstraZeneca, TESARO (Inst), VBL Therapeutics, Merck, Aravive, Eisai, Vavotar Life Sciences, Mersana (Inst), Myriad Genetics, Alkemeres (Inst), Blueprint Pharmacetuicals (Inst), GlaxoSmithKline/Tesaro (Inst), I-Mab (Inst), InxMed (Inst), Mereo BioPharma (Inst), OncXerna Therapeutics, Onconova Therapeutics, Mereo, BioPharma, Novartis; Research Funding: PTC Therapeutics (Inst), Lilly (Inst), Merck (Inst), Tesaro, (Inst), Genentech (Inst), Clovis Oncology (Inst), Lilly Foundation (Inst), Regeneron (Inst), Advaxis (Inst), Bristol Myers Squibb (Inst), Verastem (Inst), Novartis Pharmaceuticals UK Ltd (Inst), AstraZeneca (Inst), Agenus (Inst), Takeda (Inst), Forty Seven (Inst), Stem CentRx (Inst), Immunogen (Inst), Bayer (Inst), Novogen (Inst), AbbVie/Stemcentrx (Inst), artios (Inst), Bolt Biotherapeutics (Inst), Amgen (Inst), Daiichi Sankyo/Lilly (Inst), Cyteir (Inst), Immunocore (Inst) Patents, Royalties, Other Intellectual Property: UpToDate; Other Relationship: GOG Partners (Inst). RLC: Grants or contracts: Clovis Oncology, AstraZeneca, Gateway Foundation, Genelux, Genmab, Janssen, Merck, and Roche/Genentech; Consulting fees: Clovis Oncology, Agenus, Alkermes, AstraZeneca, Deciphera, Genelux, Genmab, GlaxoSmithKline, Immunogen, Janssen, OncoQuest, OncXerna, Onxeo, Regeneron, and Roche/Genentech., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)