Abstract 1073P
Background
A key issue for adjuvant melanoma patients is how they weigh the potential benefits of treatment and QOL. We assessed QOL in S1404, a trial of adjuvant pembrolizumab versus either high-dose interferon-alfa 2b (HDI) or ipilimumab.
Methods
QOL was required for patients able to complete questionnaires in English, Spanish, or French and was obtained on treatment at cycles 1, 3, 5, 7, 9 (corresponding to weeks 4, 13, 25, 37, 49) using the Functional Assessment of Cancer Therapy (FACT) Biological Response Modifiers (FACT-BRM), FACT-General (FACT-G), Functional Assessment of Chronic Illness Therapy-Diarrhea (FACIT-D), and the EuroQol EQ-5D-3L scales. The primary endpoint was the cycle 3 FACT-BRM trial outcome index (TOI). Linear regression was used to compare FACT-BRM TOI scores by arm. Linear mixed models were used to evaluate QOL scores over time, with pattern mixture models performed to account for missing data. Regression analyses included adjustments for the baseline score, disease stage and PD-L1 status. Based on the literature, a clinically meaningful difference of 5 points was targeted.
Results
Among 1303 eligible patients, 1188 (91.1%) had baseline FACT-BRM TOI scores. Patients were predominantly <65 years (74.2%) and male (59.5%); 82.4% had positive PD-L1 status. For the primary endpoint, 842 patients were evaluable (ipilimumab/HDI, 267; pembrolizumab, 565). Estimates of FACT-BRM TOI cycle 3 compliance did not differ by arm (ipilimumab/HDI, 96.0% vs. pembrolizumab, 98.3%, p=0.25). The adjusted cycle 3 FACT-BRM TOI score was 9.6 points (95% CI, 7.9 to 11.3; P<0.001) higher (better quality of life) for patients on the pembrolizumab arm compared to the ipilimumab/HDI arm, exceeding the pre-specified clinically meaningful difference. In longitudinal analyses, differences by arm exceeded 5 points in favor of pembrolizumab for each cycle except cycle 9. Results were consistent in pattern mixture models. In post-hoc analyses, FACT-BRM TOI scores favored the pembrolizumab arm compared to patients receiving either adjuvant HDI (17 points, 95% CI, 14.6-19.4, p<0.001) or ipilimumab (6 points, 95% CI, 4.1-7.8, p<0.001).
Conclusions
Adjuvant pembrolizumab results in an improved QOL over adjuvant HDI or ipilimumab.
Clinical trial identification
S1404 (NCT02506153) 15-Oct-2015.
Editorial acknowledgement
Legal entity responsible for the study
SWOG.
Funding
Southwest Oncology Group (SWOG); CTEP / NCTN; NIH / NCI grant awards: UG1CA189974, U10CA180888, U10CA180819.
Disclosure
S. Patel: Financial Interests, Personal, Invited Speaker, Peer Discussion Group leader (non-promotional): Merck & Co; Financial Interests, Personal, Proprietary Information, Independent Data Monitoring Committee Chair: Immunocore; Financial Interests, Personal, Advisory Board: TriSalus; Financial Interests, Personal, Advisory Board: Cardinal Health; Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator: Lvgen; Financial Interests, Institutional, Principal Investigator: Ideaya; Financial Interests, Institutional, Principal Investigator: Provectus; Financial Interests, Institutional, Principal Investigator: Foghorn Therapeutics. M. Othus: Financial Interests, Personal, Advisory Role, Consultant: Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Consultant: Biosight; Financial Interests, Personal, Advisory Role, Consultant: Merck; Financial Interests, Personal, Proprietary Information, Independent Data Safety Monitoring Board: Celgene; Financial Interests, Personal, Proprietary Information, Independent Data Safety Monitoring Board: Glycomimetics. A.A. Tarhini: Financial Interests, Institutional, Funding: Merck & Co; Financial Interests, Institutional, Funding: OncoSec; Financial Interests, Institutional, Funding: Genentech-Roche; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Clinigen; Financial Interests, Personal, Advisory Board: Merck & Co; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Genentech-Roche; Financial Interests, Personal, Advisory Board: Array; Financial Interests, Personal, Advisory Board: Partner Therapeutics; Financial Interests, Personal, Advisory Board: Sanofi-Genzyme/Regeneron; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: NewLink Genetics; Financial Interests, Personal, Advisory Board: BioNTech; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Advisory Board: Eisai. J.M. Kirkwood: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: CheckMate; Financial Interests, Personal, Advisory Board: Harbour BioMed; Financial Interests, Personal, Advisory Board: Iovance; Financial Interests, Personal, Advisory Board: Istari; Financial Interests, Personal, Advisory Board: OncoSec; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Elsevier; Financial Interests, Personal, Advisory Board: OncoCyte; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Advisory Board: Natera; Financial Interests, Personal, Proprietary Information, Data Safety Monitoring Board: Cytel. V. Sondak: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Replimmune; Financial Interests, Personal, Proprietary Information, Independent Data Safety Monitoring Board: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Neogene Therapeutics. A. Ribas: Financial Interests, Personal, Advisory Role, Consultant: Amgen; Financial Interests, Personal, Advisory Role, Consultant: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role, Consultant: Chugai; Financial Interests, Personal, Advisory Role, Consultant: Genentech; Financial Interests, Personal, Advisory Role, Consultant: Merck & Co; Financial Interests, Personal, Advisory Role, Consultant: Novartis; Financial Interests, Personal, Advisory Role, Consultant: Roche; Financial Interests, Personal, Advisory Role, Consultant: Sanofi; Financial Interests, Personal, Advisory Role, Consultant: Vedanta; Financial Interests, Personal, Advisory Board, Stock shares: Advaxis; Financial Interests, Personal, Advisory Board, Stock shares: Apricity; Financial Interests, Personal, Advisory Board, Stock shares: Arcus; Financial Interests, Personal, Advisory Board, Stock shares: Compugen; Financial Interests, Personal, Advisory Board, Stock shares: CytomX; Financial Interests, Personal, Advisory Board, Stock shares: Five Prime; Financial Interests, Personal, Advisory Board, Stock share: Highlight; Financial Interests, Personal, Advisory Board, Stock shares: ImaginAb; Financial Interests, Personal, Advisory Board, Stock shares: Isoplexis; Financial Interests, Personal, Advisory Board, Stock shares: Kalthera; Financial Interests, Personal, Advisory Board, Stock shares: Kite-Gilead; Financial Interests, Personal, Advisory Board, Stock shares: Merus; Financial Interests, Personal, Advisory Board, Stock shares: PACT Pharma; Financial Interests, Personal, Advisory Board, Stock shares: RAPT; Financial Interests, Personal, Advisory Board, Stock shares: Rgenix; Financial Interests, Personal, Advisory Board, Stock shares: Tango; Financial Interests, Institutional, Funding: Agilent; Financial Interests, Institutional, Funding: Bristol-Myers Squibb. K.F. Grossmann: Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Iovance; Financial Interests, Personal, Advisory Role: Array. All other authors have declared no conflicts of interest.