Abstract
BACKGROUND: Targeted therapies in the treatment of metastatic colorectal cancer (mCRC) have reportedly been associated with better quality of life (QoL). Previous studies have revealed uncontrolled sources of biases or confounders that could distort this association. Given the lack of robust evidence and causal inference, we aimed to investigate the effects of targeted therapy-added regimens versus cytotoxic therapy (CyT) on QoL and components of QoL in patients with mCRC eligible for curative-intent treatment. METHODS: We conducted a prospective cohort study on adults undergoing curative-intent mCRC treatment with survival prognosis of ≥ 1 year. The exposure was either CyT alone (including CAPEOX, mFOLFOX-6, mFOLFOX-7, FOLFIRI, and FOLFOXIRI) or CyT combined with targeted therapy (Cy-TaT, including CAPEOX-TaT, mFOLFOX-6-TaT, mFOLFOX-7-TaT, FOLFIRI-TaT, and FOLFOXIRI-TaT). Available targeted therapies included bevacizumab and regorafenib. The primary outcome was overall health and QoL (H/QoL), measured at month 12 using the EORTC QLQ-C30 global health status/QoL scale (in percentage point) and the EQ-5D-3L utility score. The secondary outcomes included each component of the EORTC QLQ-C30 functional scales and symptom scales/items (in percentage point), measured at month 12. Mean difference (MD) and 95% confidence interval (95% CI) were estimated using g-estimation. RESULTS: During 12 months of follow-up, among 1143 participants (mean age 58.1, 39.4% being female, 623 in CyT group and 520 in Cy-TaT group), overall H/QoL was higher in those receiving Cy-TaT (EORTC QLQ-C30 global health status/QoL scale: MD 16.6, 95% CI 14.8 to 18.4, p < 0.001 [largest effect in CAPEOX-TaT versus CAPEOX: MD 18.7, 95% CI 15.2 to 22.2]; EQ-5D-3L utility score: MD 0.076, 95% CI 0.060 to 0.091 [largest effect in mFOLFOX-7-TaT versus mFOLFOX-7: MD 0.123, 95% CI 0.085 to 0.161]). For the EORTC QLQ-C30 functional scales and most areas of the symptom scales/items, treatment with Cy-TaT was also associated with better outcomes than with CyT, except for a contradictory association in financial difficulties. Symptoms with consistently large improvements from Cy-TaT were fatigue (MD 13.8, 95% CI 11.7 to 15.9), dyspnoea (MD 10.9, 95% CI 8.8 to 12.9), and insomnia (MD 13.0, 95% CI 10.2 to 15.7). CONCLUSION: Compared with those on CyT alone, patients with mCRC receiving Cy-TaT showed improved overall H/QoL, functional scales, and symptom scales/items. These benefits were consistent across most subgroups of chemotherapy, with the greatest improvements in H/QoL observed in the CAPEOX-TaT and mFOLFOX-7-TaT groups.