Health-related quality of life in patients with CLDN18.2-positive, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: results from the SPOTLIGHT and GLOW clinical trials

Abstract

Background: First-line zolbetuximab plus chemotherapy (SPOTLIGHT, mFOLFOX6; GLOW, CAPOX) significantly improved progression-free survival (PFS) and overall survival (OS) versus placebo plus chemotherapy in patients with human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors were claudin 18 isoform 2-positive in the phase III SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies. We present patient-reported outcomes (PROs) from these studies.

Materials and methods: Health-related quality of life (HRQoL) was measured in the full analysis sets using the European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients Core Questionnaire (QLQ-C30) and Oesophago-Gastric Module (QLQ-OG25), Global Pain, and 5-level EQ-5D (EQ-5D-5L) questionnaires. Analyses focused on key PRO domains: global health status (GHS)/QoL, physical functioning, abdominal pain and discomfort, and nausea/vomiting. Least squares mean (LSM) changes from baseline and time to first definitive deterioration (TTDD) were evaluated combined across SPOTLIGHT and GLOW and for individual studies. Time to confirmed deterioration (TTCD) was evaluated independently for SPOTLIGHT and GLOW.

Results: The combined analysis set included 1072 patients (zolbetuximab plus chemotherapy, 537; placebo plus chemotherapy, 535). Compliance rates were similar between treatment arms. Similar trends were observed in the zolbetuximab versus placebo arms for LSM changes from baseline in key PRO domains, with no clinically meaningful deterioration. Nausea/vomiting worsened during the first few zolbetuximab cycles but later returned to baseline levels. Overall TTCD and TTDD results were similar between arms in both studies.

Conclusions: Patients in SPOTLIGHT and GLOW maintained measured HRQoL relative to baseline when treated with first-line zolbetuximab added to chemotherapy. Zolbetuximab plus chemotherapy improved PFS and OS without negatively affecting HRQoL in key PRO domains compared with placebo plus chemotherapy.

Keywords: CLDN18.2; gastric adenocarcinoma; gastroesophageal junction adenocarcinoma; patient-reported outcomes; quality of life; zolbetuximab.

Figure 1

LSM changes from baseline in PRO scores across SPOTLIGHT and GLOW. (A) GHS/QoL. (B) Physical functioning. (C) Abdominal pain and discomfort. (D) Nausea/vomiting. Dashed lines represent the within-group thresholds for clinically meaningful deterioration. Per EORTC assessments, positive LSM change from baseline indicates improvement in GHS/QoL and physical functioning; negative LSM change from baseline indicates improvement in abdominal pain and discomfort and nausea/vomiting. CI, confidence interval; EORTC, European Organisation for Research and Treatment of Cancer; GHS, global health status; LSM, least squares mean; PRO, patient-reported outcome; QoL, quality of life.

Figure 2

Kaplan–Meier plots of TTDD based on primary threshold across SPOTLIGHT and GLOW.^a,b(A) GHS/QoL. (B) Physical functioning. (C) Abdominal pain and discomfort. (D) Nausea/vomiting. Black horizontal lines represent the median threshold.^aDeaths were treated as censored events.^bTTDD was defined as the time from randomization to the first deterioration of ≥1 within-patient threshold unit compared to baseline and observed at all timepoints thereafter or followed by drop-out resulting in missing data. CI, confidence interval; GHS, global health status; HR, hazard ratio; NR, not reached; QoL, quality of life; TTDD, time to first definitive deterioration.