PD-L1-stratified health-related quality of life in solid tumors: pembrolizumab versus chemotherapy-a narrative review

The introduction of immune checkpoint inhibitors has transformed therapeutic strategies for multiple solid malignancies, with pembrolizumab emerging as a key treatment option. It is used as monotherapy in patients with high programmed death-ligand 1 (PD-L1) expression and in combination with chemotherapy in broader clinical settings. Although survival benefits are well established, understanding the impact of these treatment approaches on health-related quality of life (HRQoL) is essential for long-term cancer care. This review aims to summarize and compare HRQoL outcomes in patients with solid tumors receiving pembrolizumab monotherapy versus combination chemotherapy, while considering disease-specific PD-L1 scoring systems (tumor proportion score [TPS] and combined positive score [CPS]) and expression thresholds to support personalized treatment strategies. This narrative review synthesized evidence from randomized controlled trials, observational studies, meta-analyses, and real-world analyses identified through literature searches of major databases, including PubMed, Scopus, and Google Scholar, focusing on studies reporting HRQoL outcomes in patients receiving pembrolizumab-based therapies. A total of 64 studies were included in this narrative review. Across the included studies, HRQoL findings were heterogeneous because of differences in assessment instruments, follow-up time points, and endpoint definitions. Pembrolizumab monotherapy was commonly associated with HRQoL maintenance, delayed deterioration, or improvement in selected HRQoL domains, particularly in disease settings where pembrolizumab monotherapy is indicated for patients with higher PD-L1 expression. In contrast, combination chemotherapy was frequently associated with an early decline in HRQoL attributable to treatment-related toxicity, followed by stabilization or partial recovery, reflecting long-term functional preservation in patients achieving disease control. Overall, HRQoL outcomes varied according to tumor type, PD-L1 scoring framework, baseline symptom burden, assessment timing, and the specific HRQoL endpoint evaluated. Pembrolizumab-based therapy plays a pivotal role in modern oncology by improving survival while maintaining favorable HRQoL outcomes in appropriately selected patients. However, direct comparisons between pembrolizumab monotherapy and combination chemotherapy should be interpreted cautiously because differences in HRQoL instruments, assessment timing, endpoint definitions, and disease-specific PD-L1 assessment methodologies may contribute to the observed findings. Disease-specific PD-L1-guided treatment selection may help balance therapeutic efficacy with patient well-being; however, HRQoL findings should be interpreted within tumor-specific PD-L1 frameworks rather than as evidence of a uniform PD-L1-driven effect across all solid tumors. Future research should prioritize prospective head-to-head HRQoL comparisons using standardized HRQoL instruments, harmonized endpoint definitions, consistent assessment schedules, and disease-specific PD-L1-stratified analyses across tumor types to optimize patient-centered treatment strategies.