ABSTRACT
Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the EU as a monotherapy in patients (pts) with dMMR/MSI-H AR EC that has progressed on or after platinum-based chemotherapy;and in the US as a monotherapy in pts with dMMR AR EC that has progressed on or after platinum-based chemotherapy or dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options. We report on PFS and OS in 2 expansion cohorts of the GARNET trial that enrolled pts with EC. Methods: GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (dMMR/MSI-H EC) or A2 (MMRp/MSS EC) based on local immunohistochemistry assessment. Pts received 500 mg of dostarlimab IV every 3 weeks for 4 cycles, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal. PFS and OS are secondary efficacy endpoints. Results: 153 pts with dMMR/MSI-H and 161 pts with MMRp/MSS EC were enrolled and treated. The efficacy-evaluable population included 143 pts with dMMR/MSI-H EC and 156 pts with MMRp/MSS EC with measurable disease at baseline and ≥6 mo of follow-up. Median follow-up was 27.6 mo for dMMR/MSI-H and 33.0 mo for MMRp/MSS EC (Table). For pts with dMMR/MSI-H EC, median PFS (mPFS) was 6.0 mo, with 3-year estimated PFS rate of 40.1%. With 37.3% of pts experiencing an event, mOS was not reached;estimated 3-year OS was >50%. For pts with MMRp/MSS EC, mPFS was 2.7 mo. mOS was 16.9 mo with 68.9% of pts experiencing an event. Safety has been previously reported. [Formula presented] Conclusions: Dostarlimab demonstrated durable antitumor activity in dMMR/MSI-H and MMRp/MSS AR EC. dMMR/MSI-H was associated with longer PFS and OS than MMRp/MSS as expected. Clinical trial identification: NCT02715284. Editorial acknowledgement: Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Heather Ostendorff-Bach, PhD, of GlaxoSmithKline, was provided by Shannon Morgan-Pelosi, PhD, and Jennifer Robertson, PhD, of Ashfield MedComms, an Ashfield Health company (Middletown, CT, USA). Legal entity responsible for the study: GlaxoSmithKline. Funding: GlaxoSmithKline. Disclosure: A.V. Tinker: Financial Interests, Institutional, Sponsor/Funding: AstraZeneca;Financial Interests, Personal, Other: AstraZeneca, Eisai, GlaxoSmithKline. B. Pothuri: Financial Interests, Institutional, Funding: AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Takeda Pharmaceuticals, Tesaro/GSK;Financial Interests, Personal, Other: Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, Imab, Mersana, Tesaro/GSK, Merck, Sutro Biopharma, Tora, GOG Partners;Financial Interests, Personal, Advisory Board: Arquer Diagnostics, AstraZeneca, Atossa, Deciphera, Clovis Oncology, Eisai, Elevar Therapeutics, Imab, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, Toray;Financial Interests, Personal, Leadership Role: GOG Partners, NYOB Society Secretary, SGO Clinical Practice Committee Chair, SGO COVID-19 Taskforce Co-Chair. L. Gilbert: Financial Interests, Institutional, Funding: Alkermes, AstraZeneca, Clovis, Esperas, IMV, ImmunoGen Inc, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, Tesaro;Financial Interests, Personal, Other: Merck, Alkermes, AstraZeneca, Eisai, Eisai-Merck, GlaxoSmithKline. R. Sabatier: Financial Interests, Institutional, Funding: AstraZeneca, Eisai;Financial Interests, Personal, Other: AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, Roche;Non-Financial Interests, Personal, Other: AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Roche. J. Brown: Financial Interests, Personal, Advisory Role: Caris, Clovis, Eisai, GlaxoSmithKline;Financial Interests, Personal, Funding: GlaxoSmithKline, Genentech. S. Ghamande: Financial Interests, Personal, Advisory Role: Seattle Genetics;Financial Interests, Personal, Speaker’s Bureau: GlaxoSmithKline;Financial Interests, Institutional, Funding: Abbv e, Advaxis, Bristol Myers Squibb, Clovis, Genentech, GlaxoSmithKline, Merck, Roche, Seattle Genetics, Takeda. C. Mathews: Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Deciphera, Moderna, GSK, Regeneron, Seattle Genetics;Financial Interests, Personal, Advisory Board: IMAB biopharma. D. O'Malley: Financial Interests, Personal, Advisory Board: AstraZeneca, Tesaro/GSK, Immunogen, Ambry, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, GOGFoundation, Iovance, Eisai, Agenus, Merck, SeaGen, Novartis, Mersana, Clovis, Elevar, Takeda, Toray, INXMED, SDP Oncology (BBI), Arquer Diagnostics, Roche Diagnostics MSA, Sorrento, Corcept Therapeutics, Celsion Corp;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 Squibb Co, Serono Inc, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc, inVentiv Health Clinical, Iovance, PRA Intl, Eisai, Agenus, Merck, GenMab, SeaGen, Mersana, Clovis, SDP Oncology (BBI);Financial Interests, Personal, Other: Myriad Genetics, Tarveda. V. Boni: Financial Interests, Personal, Advisory Board: OncoArt, Guidepoint Global;Financial Interests, Personal, Speaker’s Bureau: Solti;Financial Interests, Personal, Other: START, Loxo, IDEAYA Biosciences;Financial Interests, Institutional, Research Grant: Sanofi, Seattle Genetics, Loxo, Novartis, CytomX Therapeutics, Pumo Biotechnology, Kura Oncology, GlaxoSmithKline, Roche/Genentech, Bristol-Myers Squibb, Menarini, Synthon, Janssen Oncology, Merck, Lilly, Merus, Pfizer, Bayer, Incyte, Merus, Zenith Epigenetics, Genmab, AstraZeneca, Seattle Genetics, Adaptimmune, Alkermes, Amgen, Array BioPharma, Boehringer Ingelheim, BioNTech AG, Boston Biomedical. A. Gravina: Financial Interests, Personal, Other: Gentili, Pfizer. S. Banerjee: Financial Interests, Personal, Advisory Board: Amgen, Genmab, Immunogen, Mersana, Merck Sereno, MSD, Roche, Tesaro, AstraZeneca, GSK, Oncxerna;Financial Interests, Personal, Invited Speaker: Clovis, Pfizer, Tesaro, AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview;Financial Interests, Personal, Stocks/Shares: PerciHealth;Financial Interests, Institutional, Research Grant: AstraZeneca, GSK, Tesaro;Non-Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem;Non-Financial Interests, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored): Astrazeneca;Non-Financial Interests, Advisory Role: Epsilogen;Non-Financial Interests, Other, Member of membership committee: ESGO;Non-Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity;Non-Financial Interests, Other, Received research funding from UK based charity I have provided medical advice (non-remunerated): Lady GardenFoundation Charity. R. Miller: Financial Interests, Personal, Other: AZD, Clovis Oncology, Ellipses, GlaxoSmithKline, MSD, Shionogi, AZD, GlaxoSmithKline;Financial Interests, Personal, Speaker’s Bureau: AZD, Clovis Oncology, GSK, Roche. J. Pikiel: Financial Interests, Personal, Other: Amgen, Clovis Oncology, GlaxoSmithKline, Incyte, Novartis, Odonate Therapeutics, Pfizer, Regeneron, Roche. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab;Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Karyopharm;Financial Interests, Personal, Stocks/Shares: Karyopharm;Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, ultimovacs, Apexigen;Financial Interests, Institutional, Invited Speaker: Deciphera;Non-Financial Interests, Advisory Role: Ultimovacs, Apexigen. T. Duan: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. G. Antony: Financial Interests, Personal, Fu l or part-time Employment: GlaxoSmithKline. S. Zildjian: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. E. Zografos: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. J. Veneris: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. 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.
ABSTRACT
Purpose: One in two Canadians will be diagnosed with cancer in their lifetime. With a growing proportion of patients under the age of 60, it is estimated that upwards of 25% of cancer patients are managing the demands of childbearing and parenting alongside their diagnosis. There is a paucity of research detailing how parents with cancer balance their needs with the needs of their children. This study aims to more completely define the childcare needs and perspectives of cancer patients with dependent children. Materials and Methods: Between December 2020 and February 2021, cancer patients at one major Canadian Cancer Centre, who identified as primary caregiver to at least 1 dependent (<18 years of age) were invited to partake in a survey study. The survey was developed through consultation with a multidisciplinary team and best survey practices, and consisted of 34 closed and open-ended questions designed to assess childcare needs and the experiences of cancer patients with dependent children. Specific questions were also designed to assess the impact of COVID-19 on childcare needs. Eligible participants were identified by a research assistant and presented the opportunity to complete an electronic or paper-based survey. This study was approved by the local Research Ethics Board. Results: As of February 2021, 42 patients had been contacted and 29 had completed the survey in full (69%) Participants were an average age of 44.7 years ± 4.8 years and 97% female (28/29). Twenty-two participants (76%) reported diagnoses of breast cancer. Participants reported caring for two (18/29), one (10/29), or three (1/29) children. The average age of participants' children was 8.4 years, and ranged from 8 months to 18 years. Fourteen participants (48%) indicated having to reschedule appointments due to issues with childcare (nine of 14 rescheduling 1-3 appt.;4/14, 4-6 appt.;one of 14, 10+ appt.). Additionally, 11 participants (38%) reported bringing their child or children to their appointments as a solution for issues with childcare (seven of 11 for 1-3 appt.;three of 11, 4-6 appt.;one of 11, 10+ appt.). Fourteen of 26 respondents (54%) indicated that balancing childcare throughout their cancer journey has had a moderate (eight of 26) or extreme (six of 26) impact on their stress levels. Sixty-one percent (17/28) reported that the COVID-19 Pandemic has impacted their childcare needs and impacted their stress levels moderately (10/17) or extremely (three of 17). Seventy-eight percent (21/27) reported that a flexible childcare service would allow them to more regularly attend their appointments. The preferred delivery of such a program was onsite (hospital or cancer centre) (13/20, 65%), followed by in-home (seven of 20, 35%). Narrative analysis noted themes of increased stress and childcare responsibilities associated with the COVID-19 Pandemic and reduction of childcare resources and support. Conclusions: These preliminary results indicate that childcare issues are broadly impactful for parents battling cancer. The lack of supportive childcare negatively impacts the emotional psychological well-being of patients and their children, as well as impacts system efficiency and treatment compliance. Survey accrual is continuing and complete findings will aid in defining the childcare needs and perspectives of parents with cancer, as well as highlight potential solutions to support these individuals.