SO-8 Health-related Quality of Life in Patients Treated with Pembrolizumab for Microsatellite Instability-High/mismatch Repair Deficient Advanced Solid Tumors: Results from the KEYNOTE-158 Study

Approval of pembrolizumab (200 mg Q3W) for the treatment of unresectable or metastatic microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) solid tumors that progressed on prior therapy was based on results from the phase 2, open-label, multicohort, KEYNOTE-158 study (NCT02628067). Pembrolizumab demonstrated a high ORR (primary endpoint) and durable clinical benefit in this population. We present Health-related quality of life (HRQoL) results (exploratory endpoints) from the MSI-H/dMMR population (cohort K). Patients enrolled in cohort K of KEYNOTE-158 had previously treated MSI-H/dMMR advanced noncolorectal solid tumors, measurable disease per RECIST v1.1, and ECOG performance status of 0–1. Patients received pembrolizumab 200 mg Q3W for up to 35 cycles (2 years) or until disease progression, unacceptable toxicity, or patient withdrawal. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and the EuroQol group EQ-5D-3L questionnaires were administered at baseline, regular intervals throughout treatment, and 30 days after treatment discontinuation. Prespecified analyses included change from baseline in all patients overall 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) score; and the proportion of patients who had QLQ-C30 scores that “improved”/”worsened” (defined as ≥10 points change) or “remained stable” from baseline. At data cutoff (October 5, 2020), 351 patients were enrolled in cohort K. 311 and 315 patients completed baseline QLQ-C30 and EQ-5D-3L questionnaires, respectively. Compliance rates were 93% and 94%, respectively, out of the 334 patients expected to complete the questionnaires at baseline, and 88% out of 279 patients at week 9 for both questionnaires. QLQ-C30 GHS/QoL scores (mean [95% CI] change from baseline) improved at week 9 (3.07 [0.19‒5.94]) and remained stable or improved over time through week 111, with greater improvements observed in patients with best overall response of CR or PR (10.85 [6.36‒15.35]). Improvements were observed in role functioning (4.26 [0.61‒7.90]) whereas no differences were observed for social (1.88 [−1.67 to 5.42]), emotional (1.19 [−1.28 to 3.66]), physical (−0.06 [−2.54 to 2.42]), and cognitive (−2.09 [−4.44 to 0.25]) functioning. Patients with CR/PR showed improvements in physical (5.58 [1.91‒9.25]), role (9.88 [3.80‒15.97]), emotional (5.62 [1.56‒9.68]), and social (8.33 [2.70‒13.97]) functioning; no differences were observed for cognitive functioning (1.74 [−1.45 to 4.94]). Symptoms that showed improvements in all patients included pain (−4.69 [−8.46 to −0.92]), insomnia (−4.76 [−8.52 to −1.00]), and appetite loss (−4.47 [−8.15 to −0.79]). Over 70% of patients experienced either improved or stable scores at week 9 for GHS/QoL (improved, 32.0%; stable, 45.9%) and all functional and symptom scales/items. Largest improvements were seen for fatigue (40.3%), pain (39.8%), role functioning (35.1%), social functioning (29.9%), insomnia (28.6%), and appetite loss (28.1%). Slight improvements were observed in EQ-5D VAS scores (mean [95% CI] change from baseline at week 9) in the overall population (2.88 [0.72‒5.03]), whereas patients with CR/PR experienced larger improvements (6.74 [3.51‒9.96]). Mean EQ-5D VAS scores remained stable or improved over time through week 111. Pembrolizumab generally improved or preserved HRQoL in patients with previously treated MSI-H/dMMR advanced noncolorectal solid tumors.