ABSTRACT Some new oncology drugs offer substantial patient health benefit. However, due to high costs, many remain unavailable to patients in low‐ and middle‐income countries. Next to exorbitant drug pricing, uncertainty of the magnitude of benefit of new treatments can contribute to differences in global access to cancer treatments, even in high‐income countries. Health technology assessment (HTA) organizations employ predetermined criteria to assess whether a drug's efficacy suffices for local approval, ideally informed by randomized controlled trials (RCTs) that provide data on the clinically relevant endpoints overall survival (OS) and quality of life (QoL). Contemporary oncology RCTs increasingly suffer from design and interpretation issues that lead to inadequate data for HTA assessments. The Keynote‐177 RCT was the landmark study demonstrating the superiority of pembrolizumab over chemotherapy in terms of progression free survival and subsequently OS, as a first‐line treatment for patients with metastatic microsatellite instable high (MSI) colorectal cancer (CRC). However, in a trial testing the initial efficacy of immunotherapy in advanced MSI CRC, the allowance of crossover delayed the OS signal. Along with other design‐related limitations, this complicates the precise determination of the absolute benefit of first‐line immunotherapy on OS or quality of life in advanced MSI CRC.
Gerritse et al. (Wed,) studied this question.