A recent retrospective study has shed light on the feasibility and tolerability of PD-1 blockades in elderly patients with metastatic esophageal squamous cell carcinoma (ESCC). The study, conducted at Tianjin Medical University Cancer Institute and Hospital, aimed to provide real-world evidence on the effectiveness and safety of PD-1 blockade monotherapy in this often-underrepresented population. The findings suggest that PD-1 blockades could be a viable therapeutic option for elderly patients with previously treated metastatic ESCC, offering valuable guidance for clinical practice.
The study included 78 patients aged 65 years or older who received PD-1 blockade monotherapy between October 2018 and January 2023. The primary endpoint was overall survival (OS), with secondary endpoints including objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and safety profile. The median age of the patients was 73 years (range: 65-87 years), and all patients had previously undergone at least one systemic treatment regimen.
Efficacy of PD-1 Blockade
The results showed an ORR of 23.1% (95% CI: 14.3-34.0%) and a DCR of 56.4% (95% CI: 44.7-67.6%). The median DOR among the 18 patients who achieved a partial response (PR) was 8.8 months (95% CI: 5.99-11.61). The median PFS was 3.1 months (95% CI: 1.64-4.56), and the median OS was 10.9 months (95% CI: 6.02-15.78).
Prognostic Factors
Interestingly, ECOG performance status and the number of metastatic lesions were identified as independent prognostic factors for OS. Patients with an ECOG performance status of 0-1 had a longer OS compared to those with a score of 2 (12.2 vs 8.2 months, P = 0.014). Similarly, patients with ≤3 metastatic lesions had a better OS than those with >3 metastatic lesions (12.2 vs 7.8 months, P = 0.012).
Safety Profile
The safety profile of PD-1 blockades in this elderly population was generally acceptable, although the incidence of adverse reactions was slightly higher compared to previous clinical trials. A total of 61 patients (78.2%) experienced adverse reactions of any grade, with 16 patients (20.5%) experiencing grade ≥3 adverse reactions. The most common adverse reactions included fatigue (32.1%), gastrointestinal reactions (24.4%), and diarrhea (19.2%).
Implications and Future Directions
"Our study provides real-world evidence regarding the effectiveness and tolerability of PD-1 blockade monotherapy for elderly patients with ESCC," the authors noted. "These findings suggest that patients with lower ECOG performance status scores and fewer metastatic sites might derive greater benefit from PD-1 blockades."
However, the authors also cautioned about the limitations of the study, including its retrospective design and relatively small sample size. They emphasized the need for future prospective studies with larger cohorts to validate these findings and explore additional biomarkers that may further refine prognostic assessments.
Despite these limitations, the study offers valuable insights into the management of elderly patients with metastatic ESCC and highlights the potential of PD-1 blockades as a therapeutic option in this challenging population.
