Dr Elez on the Rationale for Evaluating QOL Outcomes With ICI Doublets in mCRC

"When we are using a doublet and adding an extra drug, we have this potential to have even maybe more toxicity, but no other impact in terms of quality of life. [Instead], we see there is a trend of improvement for those patients [who received the doublet]."

Elena Élez, MD, PhD, a medical oncology consultant at Vall d’Hebron University Hospital and a senior investigator at Vall d’Hebron Institute of Oncology, discussed the rationale for evaluating the role of, and quality of life (QOL) outcomes with, combination checkpoint blockade in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) through the phase 3 CheckMate 8HW trial (NCT04008030).

Recent studies in mCRC have focused on optimizing post-induction treatment strategies and refining frontline immunotherapy for microsatellite instability-high (MSI-H) disease, Elez began.

One such study is the CheckMate 8HW trial, which evaluated nivolumab (Opdivo) plus ipilimumab (Yervoy) vs nivolumab in patients with MSI-H mCRC. The study had previously reported data showing the superiority of the nivolumab and ipilimumab combination compared to chemotherapy. The awaited comparison was between the doublet and nivolumab monotherapy, and the recently presented results cover this comparison across all lines of treatment.

Findings presented during the 2025 ESMO Gastrointestinal Cancers Congress revealed that patients receiving the doublet regimen (n = 296) achieved a significant progression-free survival (PFS) benefit when compared with those who received nivolumab monotherapy (n = 286; HR, 0.62; 95% CI, 0.48-0.81; P = .0003). Élez emphasized that a critical part of the recent presentation was the quality-of-life data comparing the doublet against the monotherapy.

Although the use of a doublet adds the potential for increased toxicity, the trial showed that patients in the investigational arm experienced a numerical benefit in terms of QOL, depending on the scale used. Élez noted that there was a trend favoring the doublet across several QOL assessment tools, including the EORTC QLQ-C30 (for all patients), the QLQ-CR29 (for those with CRC), and QOL (for patients with any illness). This positive trend in QOL, despite the addition of an extra drug, is considered an important outcome. Élezconcluded that they did not observe a negative impact on QOL and instead saw a trend of improvement for patients dealing with the disease, even with the addition of a second agent.