Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON)

Abstract

Objectives: In the phase 3 POSEIDON study, first-line tremelimumab plus durvalumab and chemotherapy significantly improved overall survival and progression-free survival versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC). We present patient-reported outcomes (PROs).

Patients and methods: Treatment-naïve patients were randomized 1:1:1 to tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, or chemotherapy. PROs (prespecified secondary endpoints) were assessed using the European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire version 3 (QLQ-C30) and its 13-item lung cancer module (QLQ-LC13). We analyzed time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization by log-rank test and improvement rates by logistic regression.

Results: 972/1013 (96 %) patients randomized completed baseline QLQ-C30 and QLQ-LC13 questionnaires, with scores comparable between treatment arms. Patients receiving tremelimumab plus durvalumab and chemotherapy versus chemotherapy had longer median TTD for all PRO items. Hazard ratios for TTD favored tremelimumab plus durvalumab and chemotherapy for all items except diarrhea; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, cognitive functioning, pain, nausea/vomiting, insomnia, constipation, hemoptysis, dyspnea, and pain in other parts. For durvalumab plus chemotherapy, median TTD was longer versus chemotherapy for all items except nausea/vomiting and diarrhea. Hazard ratios favored durvalumab plus chemotherapy for all items except appetite loss; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, role functioning, dyspnea, and pain in other parts. For both immunotherapy plus chemotherapy arms, improvement rates in all PRO items were numerically higher versus chemotherapy, with odds ratios > 1.

Conclusions: Tremelimumab plus durvalumab and chemotherapy delayed deterioration in symptoms, functioning, and global health status/QoL compared with chemotherapy. Together with significant improvements in survival, these results support tremelimumab plus durvalumab and chemotherapy as a first-line treatment option in metastatic NSCLC.

Keywords: Durvalumab; Health-related quality of life; Metastatic non-small-cell lung cancer; POSEIDON; Patient-reported outcomes; Tremelimumab.