Health-related quality-of-life outcomes with regorafenib in advanced gastric and esophagogastric junction cancer: results from the INTEGRATE trials.

BACKGROUND

The INTEGRATE trials evaluated regorafenib in advanced gastric and esophagogastric junction cancer (AGOC), a poor prognosis population. In INTEGRATE 1 (I1, phase 2), regorafenib improved progression-free survival (PFS) without a clear excess decline in health-related quality of life (HRQoL). INTEGRATE 2a (I2a, phase 3) demonstrated an overall survival (OS) benefit, alone and in a pre-specified pooled analysis with I1.

AIM: To evaluate HRQoL outcomes from I2a and the pooled analysis with I1.

METHODS

HRQoL was assessed at baseline, day 1 of each cycle, and every 8 weeks until progression, using EORTC QLQ-C30, EORTC STO22, and the participant Disease and Treatment Assessment (PtDATA). The primary endpoint was deterioration-free survival (DetFS), defined as time to a ≥ 10-point decline in QLQ-C30 physical function (DetFSPF) or global health status (DetFSGHS), progression, or death. Secondary analyses used linear mixed models (LMM). Tertiary analyses used logistic regression to evaluate symptom and side-effect prevalence (PtDATA). Pooled analyses adjusted for trial effects.

RESULTS

Of 251 I2a participants, 240 contributed HRQoL data. Regorafenib was superior on DetFSPF (HR = 0.75, 95% CI 0.58-0.99, p = 0.03) and DetFSGHS (HR = 0.68, 95% CI 0.52-0.89, p = 0.004). LMM showed no appreciable differences in HRQoL trajectories. Rash, hand-foot syndrome, numbness, and coping difficulties were more frequent with regorafenib. Pooled analyses confirmed these findings.

CONCLUSION

Regorafenib modestly prolonged survival in AGOC without clear HRQoL deterioration. Despite more frequent toxicities, overall HRQoL was preserved. Regorafenib may offer a net clinical benefit when survival and HRQoL preferences are considered.