Abstract 1752P
Background
First-line pembrolizumab monotherapy is a standard of care option in platinum-ineligible patients with advanced UC in the US. However, there is no standard definition of platinum ineligibility; treatment decisions are based on clinical judgment. It is of interest to determine whether efficacy of pembro in UC varies based on criteria used to define platinum ineligibility.
Methods
This post hoc analysis pooled pts treated with pembro monotherapy from KEYNOTE-052 (N=370; NCT02335424) and LEAP-011 (N=242; NCT03898180) who were potentially platinum ineligible based on criteria determined by an extensive search of the literature. Candidate criteria for platinum ineligibility identified in the literature included ECOG PS 2, renal dysfunction (GFR <60 mL/min), visceral disease, and age ≥80 y. Subgroups of pts with several combinations of these criteria were selected for this analysis: ECOG PS 2 (with or without age ≥80 y, renal dysfunction, or visceral disease); age ≥80 y with renal dysfunction; or visceral disease (with or without age ≥80 y or renal dysfunction). Efficacy end points were ORR and OS.
Results
The database cutoffs were September 26, 2020 (KEYNOTE-052), and July 26, 2021 (LEAP-011); median (range) follow-up was 56.3 mo (51.2-65.3) and 7.0 mo (0.2-25.0), respectively. In the primary analyses, ORR (95% CI) was 28.9% (24.3-33.8) in KEYNOTE-052 and 28.9% (23.3-35.1) in the pembro monotherapy arm of LEAP-011; median (95% CI) OS was 11.3 (9.7-13.1) and 12.9 (9.8-17.8) mo, respectively. ORR ranged from 23.5%-33.3%, and median OS ranged from 9.0-10.6 mo among the subgroups (Table). Table: 1752P
| Age ≥80 y + renal dysfunction n=111 | ECOG PS 2 only n=355 | ECOG PS 2 + age ≥80 y n=87 | ECOG PS 2 + renal dysfunction n=176 | ECOG PS 2 + visceral disease n=285 | Visceral disease + age ≥80 y n=116 | Visceral disease + renal dysfunction n=307 | |
| ORR, % (95% CI) | 27.9 (19.8-37.2) | 26.2 (21.7-31.1) | 33.3 (23.6-44.3) | 27.8 (21.4-35.1) | 23.5 (18.7-28.9) | 26.7 (18.9-35.7) | 25.7 (20.9-31.0) |
| OS, median (95% CI), months | 10.6 (6.8-12.3) | 10.1 (8.6-11.7) | 9.3 (6.3-12.2) | 10.1 (8.6-13.8) | 9.1 (7.2-10.8) | 9.0 (6.1-11.3) | 10.6 (9.0-12.5) |
| 12-month OS, % | 43.3 | 44.3 | 40.5 | 45.2 | 40.2 | 35.4 | 45.2 |
Conclusions
In this post hoc exploratory analysis, responses to pembro monotherapy occurred regardless of the criteria used to define platinum ineligibility for pts with UC. Median OS was generally consistent among subgroups and was similar to the overall pt populations.
Clinical trial identification
KEYNOTE-052 (NCT02335424) and LEAP-011 (NCT03898180) Release date: KEYNOTE-052 (January 9, 2015); LEAP-011 (April 1, 2019).
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Shane Walton, PhD, and Matthew Grzywacz, PhD of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Eisai Inc., Nutley, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Eisai Inc., Nutley, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Eisai Inc., Nutley, NJ, USA.
Disclosure
Y. Loriot: Financial Interests, Personal, Advisory Board: Merck Kga, Pfizer, Gilead, Seattle Genetics, Tahio; Financial Interests, Personal, Other, lectures, advisory boards: MSD, AstraZeneca, Astellas, Janssen; Financial Interests, Personal, Other, lectures, advisroy boards: Roche, BMS; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, MSD, Roche, Celsius; Financial Interests, Institutional, Invited Speaker: Janssen, Pfizer, janssen, MSD, Janssen, Exelexis, AstraZeneca, Pfizer, Merck Kga, BMS, Astellas, Gilead, Incyte; Financial Interests, Invited Speaker: MSD, Astellas, Gilead/Immunomedics, Tahio; Financial Interests, Personal, Invited Speaker: Basilea; Non-Financial Interests, Member: ESMO, ASCO, AACR; Non-Financial Interests, Other, scientific committee: ARC. N. Matsubara: Financial Interests, Personal, Invited Speaker: National Cancer Center Hospital East; Financial Interests, Personal, Speaker’s Bureau: National Cancer Center Hospital East; Financial Interests, Personal, Advisory Board: National Cancer Center Hospital East; Financial Interests, Institutional, Research Grant: National Cancer Center Hospital East; Financial Interests, Institutional, Funding: National Cancer Center Hospital East. M. Gumus: Financial Interests, Institutional, Research Grant: Istanbul Medeniyet University; Financial Interests, Institutional, Funding: Istanbul Medeniyet University; Financial Interests, Institutional, Principal Investigator: Istanbul Medeniyet University. B.B. Karaca: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Novartis, MSD; Financial Interests, Personal, Funding: MSD, Novartis. P. Grivas: Financial Interests, Personal, Other, Consulting: AstraZeneca, Astellas Pharma, Bayer, Bristol Myers Squibb, Dyania Health, EMD Serono, Exelixis, Foundation Medicine, Genentech/Roche, Genzyme, GlaxoSmithKline, Guardant Health, Gilead Sciences, Infinity Pharmaceuticals, Janssen, Lucence Health, Merck, Mir; Financial Interests, Institutional, Research Grant: Bavarian Nordic, Bristol Myers Squibb, Clovis Oncology, Debiopharm, EMD Serono, G1 Therapeutics, Gilead Sciences, GlaxoSmithKline, Merck, Mirati Therapeutics, Pfizer, QED Therapeutics. R. De Wit: Financial Interests, Personal and Institutional, Invited Speaker: Sanofi; Financial Interests, Personal and Institutional, Research Grant: Sanofi, Bayer; Financial Interests, Personal, Advisory Board: Merck, Orion, Astellas; Financial Interests, Personal and Institutional, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Astellas. A.O. Siefker-Radtke: Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Astrazeneca, Basilea, Bristol Myers Squibb, Curio, Genentech, Gilead, Ideaya, Immunomedics, Janssen, Oncology, Merck Sharp & Dohme, Natera, Nektar Therapeutics, Taiho, Seagen; Financial Interests, Personal, Funding: Basilea, Bristol Myers-Squibb, Janssen, Merck Sharpe & Dohme, Nektar Therapeutics (Clinical Trial Support); Financial Interests, Personal, Other: Basilea, Bristol Myers-Squibb, Janssen, Merck Sharpe & Dohme, Nektar Therapeutics (Clinical Trial Support). D.E. Castellano Gauna: Financial Interests, Personal, Advisory Role: Janssen Oncology, Roche/Genentech, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Ipsen, Bristol Myers Squibb, MSD Oncology, Bayer, Lilly, Sanofi, Pierre Fabre, Boehringer Ingelheim; Financial Interests, Institutional, Funding: Janssen Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer, Roche, Bristol Myers Squibb, AstraZeneca Spain. P.H. O'Donnell: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Seattle Genetics, Genentech/Roche, Janssen; Financial Interests, Personal, Other: Janssen, Nektar, NIH, Dragonfly Therapeutics, G1 Therapeutics; Financial Interests, Personal, Stocks/Shares: Allergan; Financial Interests, Personal, Other, Honoraria: Genentech/Roche; Merck; Astellas Pharma; Seattle Genetics; Atheneum; Health Advances; Janssen; Dedham Group; Pfizer; CLD, Inc.; Axiom Healthcare Strategies; EMD Serono; IntrinsiQ Specialty Solutions; ISMIE; NAMCP; Financial Interests, Institutional, Funding: Boehringer Ingelheim, Merck, Genentech/Roche, AstraZeneca/MedImmune, Acerta Pharma, Janssen, Seattle Genetics, Bristol Myers Squibb, Astellas Pharma. T.B. Powles: Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck, MSD, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, Mashup Ltd.; Financial Interests, Personal, Research Grant: AstraZeneca, BMS, Exelixis, Ipsen, Merck, MSD, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen. J. Vuky: Financial Interests, Institutional, Sponsor/Funding: Agendia, Arvinas, Astellas Pharma, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Celldex, Clovis Oncology, Deciphera, Eisai, Exelixis, Fortis, Roche/Genetech, Ignyta, Incyte, Innocrin Pharma, Lilly, Loxo, Merck, Novartis, Pfizer, Polyphor, Rgeni; Financial Interests, Personal, Advisory Board: Seattle Genetics/Astellas. Y. Zhao: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. K. O'hara: Financial Interests, Personal, Full or part-time Employment: Eisai. S. Franco: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. B. Homet Moreno: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. J. Zolnierek: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD. All other authors have declared no conflicts of interest.