Abstract 797P
Background
In cohorts D and K of the nonrandomized, open-label, phase II KEYNOTE-158 study (NCT02628067), pembro demonstrated a clinically meaningful ORR and durable responses in pts with unresectable/metastatic MSI-H/dMMR endometrial cancer (EC) who progressed on prior therapy. We present HRQoL data (exploratory endpoint) from pts with MSI-H/dMMR EC from KEYNOTE-158.
Methods
Pts from cohorts D (EC, regardless of MSI-H status) and K (any MSI-H/dMMR solid tumor, except colorectal) with previously treated, advanced MSI-H/dMMR EC received pembro 200 mg Q3W for 35 cycles. The EORTC Quality of Life Questionnaire (QLQ-C30) and the EQ-5D-3L were administered at baseline, regular intervals while on treatment, and 30 d after treatment discontinuation. Prespecified analyses included change from baseline to week 9 in all pts and by best overall response for QLQ-C30 global health status (GHS)/QoL, QLQ-C30 functional/symptom scales/items, and EQ-5D-3L visual analogue scale (VAS).
Results
At data cutoff (Oct 5, 2020), 90 pts were enrolled. 76 completed ≥1 QLQ-C30 and 79 completed ≥1 EQ-5D-3L questionnaire. Compliance rates were 90% for QLQ-C30 and 94% for EQ-5D-3L at baseline and 92% and 93% at week 9. QLQ-C30 GHS/QoL score and most functional scales were improved from baseline to week 9 in the overall population, with greater benefit in pts who achieved CR/PR. Greatest improvements in symptom scales were reported for pain, insomnia, and appetite loss (Table). Mean EQ-5D VAS scores were improved from baseline to week 9 in the overall population (6.0 [95% CI, 2.3 to 9.7]) and in pts with CR/PR (9.1 [95% CI, 5.2 to 13.0]).
Conclusions
Pembro maintained or improved HRQoL in pts with previously treated, advanced MSI-H/dMMR EC. Taken together with the durable and clinically meaningful responses, these data further support the use of pembro in this setting. Table: 797P
| Change from baseline to week 9 in QLQ-C30 scores | All PtsN = 63 | Pts With CR/PRN = 35 |
| GHS/QoL | 6.1 (0.7 to 11.5) | 11.7 (5.3 to 18.0) |
| Physical functioning | 1.9 (−3.1 to 6.9) | 6.7 (0.0 to 13.3) |
| Role functioning | −0.3 (−6.3 to 5.7) | 8.1 (1.2 to 15.0) |
| Emotional functioning | 3.3 (−1.9 to 8.5) | 8.6 (3.0 to 14.1) |
| Cognitive functioning | −0.0 (−5.0 to 5.0) | 3.8 (−1.9 to 9.5) |
| Social functioning | 4.0 (−3.5 to 11.4) | 9.0 (1.2 to 16.9) |
| Pain | −12.2 (−19.5 to −4.8) | −18.6 (−26.1 to −11.0) |
| Insomnia | −7.9 (−14.5 to −1.4) | −8.6 (−17.1 to −0.1) |
| Appetite loss | −5.3 (−12.7 to 2.1) | −17.1 (−24.7 to −9.6) |
For GHS/QoL and functional scales, a positive score indicates improvement; for symptom scales, a negative score indicates improvement.
.Clinical trial identification
NCT02628067.
Editorial acknowledgement
Writing support was provided by Christabel Wilson, MSc, of ICON plc (North Wales, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
D. O'Malley: Financial Interests, Personal, Advisory Board: AstraZeneca, Tesaro/GSK, BBI, Immunogen, Ambry, Janssen/J&J, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, GOGFoundation, Iovance Biotherapeutics, Inc, Myriad Genetics, Eisai, Agenus, Tarveda, Merck & Co., Inc., Kenilworth, NJ, USA, SeaGen, Novart; Financial Interests, Institutional, 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, NCI, Bristol Mye. G.M. Bariani: Financial Interests, Personal, Funding: Mabxience; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Libbs. P.A. Cassier: Financial Interests, Personal, Funding: Roche/Genentech; Novartis; Amgen; Bristol Myers Squibb; Blueprint Medicines; GlaxoSmithKline; Janssen; Eli Lilly; Taiho Pharmaceutical; AstraZeneca; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Celgene; AbbVie; Toray ; Financial Interests, Personal, Other, Personal fees: Roche/Genentech; Novartis; Amgen; Merck Serono; and AstraZeneca; Non-Financial Interests, Personal, Other, Nonfinancial support: Roche/Genentech; Novartis; AstraZeneca; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; and Plexxikon; Financial Interests, Personal, Other, Travel accommodations: NETRIS Pharma. A. Marabelle: Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD); Financial Interests, Personal, Other, Honorarium: MSD; Financial Interests, Personal, Research Grant: Fondation de l’Avenir and Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, MSD. A.R. Hansen: Financial Interests, Personal, Advisory Role: Genentech/Roche, Merck & Co., GSK, Bristol Myers Squibb, Novartis, Boehringer Ingelheim, AstraZeneca, MedImmune; Financial Interests, Personal, Funding: Genentech/Roche, Merck & Co., GSK, Bristol Myers Squibb, Novartis, Boehringer Ingelheim, AstraZeneca, MedImmune, Boston Medical. A. De Jesus Acosta: Financial Interests, Personal, Funding: AstraZeneca; Merck & Co., Inc., Kenilworth, NJ, USA. Consultancy for Merck & Co., Inc., Kenilworth, NJ, USA. W.H. Miller, Jr: Financial Interests, Personal, Other, Personal fees for serving as a consultant: BMS, Merck & Co., Inc., Kenilworth, NJ, USA, Roche, Novartis, Amgen, GSK, and Sanofi. A. Italiano: Financial Interests, Personal, Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; AstraZeneca; Merck Serono; and Bayer; Financial Interests, Personal, Other, Personal fees: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; AstraZeneca; Bayer; Bristol Myers Squibb; Epizyme; and Roche. M. Amonkar: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA. L. Xu: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA. F. Jin: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA. K. Norwood: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA. M. Maio: Financial Interests, Personal, Advisory Board: Roche; Bristol Myers Squibb; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Incyte; AstraZeneca; Amgen; Pierre Fabre; Eli Lilly; GlaxoSmithKline; Sanofi; Alfasigma; Merck Serono; Financial Interests, Personal, Other, Honoraria: Roche, Bristol Myers Squibb; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; AstraZeneca; Amgen; Pierre Fabre; Eli Lilly; GlaxoSmithKline; Sciclone; Sanofi; Alfasigma; Merck Serono; Financial Interests, Personal, Stocks/Shares: Epigen Therapeutics, and Theravance. All other authors have declared no conflicts of interest.