A quality-adjusted time without symptoms and toxicity (Q-TWiST) analysis comparing nivolumab plus ipilimumab or nivolumab plus chemotherapy versus chemotherapy in patients with advanced esophageal squamous-cell carcinoma in CheckMate 648

<h3>Background</h3> First-line nivolumab plus chemotherapy (NIVO + CHEMO) and nivolumab plus ipilimumab (NIVO + IPI) improves overall survival for patients with advanced esophageal squamous-cell carcinoma (ESCC). This analysis aimed to use quality-adjusted time without symptoms or toxicity (Q-TWiST) analyses to assess the overall risk–benefit profile of these treatments in the CheckMate 648 study. <h3>Materials and methods</h3> A <i>post hoc</i> analysis of CheckMate 648 assessed the association of quality-adjusted survival with treatment types (first-line NIVO + CHEMO, NIVO + IPI, or CHEMO alone) using the Q-TWiST methodology. The analysis included all randomized patients and those with tumor cell programmed death-ligand 1 (PD-L1) ≥1% at baseline, with a minimum follow-up of 45 months. Health-related quality of life was assessed using the EuroQoL 5-Dimension 3-Level (EQ-5D-3L) questionnaire. Differences in Q-TWiST exceeding 1.5 months were deemed clinically important. <h3>Results</h3> The analysis included 970 patients in the all-randomized population. Q-TWiST values were 12.8 and 12.9 months for NIVO + CHEMO and NIVO + IPI, respectively, compared with 10.8 months for CHEMO alone, showing gains of 2.0 and 2.1 months, respectively. In patients with tumor cell PD-L1 ≥1% (473 patients), Q-TWiST values were higher for NIVO + CHEMO (13.0 months) and NIVO + IPI (13.3 months) compared with CHEMO alone (9.1 months), with gains of 3.9 and 4.2 months, respectively. All gains surpassed the clinically important threshold. <h3>Conclusion</h3> These findings support NIVO + CHEMO and NIVO + IPI as first-line treatments for patients with advanced ESCC, particularly those with tumor cell PD-L1 ≥1%.