Combination Therapy with Pembrolizumab and Etoposide/Platinum for Small Cell Lung Cancer

Compared to placebo-EP as first-line therapy for ES-SCLC, pembro-EP significantly improved progression-free survival (PFS) and had no unexpected toxicities in the randomized, double-blind KEYNOTE-604 study (NCT03066778); the HR for overall survival (OS) favored pembro-EP, but the significance threshold was missed. Here we offer KEYNOTE-604 patient-reported outcomes (PROs). Pembro 200 mg Q3W or saline placebo for ≤35 cycles + 4 cycles of standard-dose EP was administered to 453 patients (pts) in a 1:1 ratio. At cycles 1-9, 11, 13, 15, 17, treatment termination, and the 30-day safety follow-up, participants completed electronic PRO questionnaires, including the EORTC QLQ-C30 and QLQ-LC13, before undergoing other trial-related procedures. A protocol-specified exploratory endpoint was time to true deterioration (TTD) in the QLQ-C30 global health status (GHS)/QoL scale. The primary study endpoint was the mean change from baseline to wk 18 in the QLQ-C30 GHS/QoL scale. Time to deterioration (TTD) was defined as the time until the first ≥10-point decline from baseline that was confirmed using the right-censoring criteria. All 439 patients who received treatment and completed at least ≥1 PRO assessment had their HRQoL measured. P values are two-sided and have a nominal value.

PRO compliance was ≥89% in both groups at baseline and wk 18. Pembro-EP participants had a mean baseline score of 60.54 on the QLQ-C30 GHS/QoL scale, while those in the placebo-EP group scored 58.37. In week 18, scores improved in both groups, with a least squares mean change from baseline (95% CI) of 8.66 points (5.26-12.06) in the pembro-EP group and a difference of 4.43 points (0.21-8.66; P =.040) in the placebo-EP group. Pembro-EP did not reach (NR) its median TTD for the QLQ-C30/LC13 composite of cough, chest discomfort, or dyspnea, but placebo-EP did (HR 0.80 [95% CI 0.56-1.14]; P =.208). Both groups had similar median TTDs on the QLQ-C30 GHS/QoL scale (HR 0.78 [95% CI 0.52-1.18]; P =.238). When comparing EP with placebo-EP as first-line therapy for ES-SCLC, adding pembro did not worsen HRQoL and may have improved it. Pembro’s effectiveness in SCLC is supported by both efficacy and safety data, as seen in the KEYNOTE-604 study, and by PRO data.

Source: https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/health-related-quality-of-life-hrqol-in-keynote-604-pembrolizumab-pembro-or-placebo-added-to-etoposide-and-platinum-ep-as-first-line-therapy

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03066778