Impact of Performance Status on Response and Survival Among Patients Receiving Checkpoint Inhibitors for Advanced Solid Tumors

Abstract

PURPOSE Clinical trials, which led to the approval of immune checkpoint inhibitors (ICI), have been almost exclusively performed in patients with good Eastern Cooperative Oncology Group performance status (ECOG PS of 0-1). However, ICI remains an attractive option for patients with advanced tumors and poor PS. We hypothesized that patients with ECOG PS ≥ 2 would have worse outcomes with ICI. METHODS We retrospectively identified patients with advanced solid tumors who were treated with ICI at our institution. The log-rank test compared the survival among patients with different ECOG PS. We used a proportional hazards model to assess association between ECOG PS and overall survival (OS) with adjustment for covariates including age, sex, malignancy type, time from advance disease diagnosis, and line of therapy. We compared overall response rates between groups with Pearson chi-square exact test. We also analyzed in-hospital mortality and hospice referral rates. RESULTS We identified 257 patients treated with ICI. One hundred eighty-two patients had ECOG PS 0-1, and 75 had ECOG PS ≥ 2. The median overall survival was 12.6 months for the ECOG PS 0-1 group compared with 3.1 months for the ECOG PS ≥ 2 group ( P < .001). The overall response rate for patients with ECOG PS 0-1 was 23% compared with 8% for those with poor PS ( P = .005). Patients with poor PS treated with ICI had similar hospice referral rates (67% for ECOG PS ≥ 2 v 61.9% for ECOG PS 0-1, P = .50) but were more likely to have in-hospital death as compared with the good PS group (28.6% v 15.1%, P = .035). CONCLUSION Despite the appeal of ICI in patients with advanced malignancy and poor PS, outcomes in this cohort were poor. Prospective trials defining the activity and role of ICI in poor PS are urgently needed.

Predicting immune‐related adverse events using a simplified frailty score in cancer patients treated with checkpoint inhibitors: A retrospective cohort study

“…Patients with ECOG PS >1 are frequently excluded from pivotal randomized trials and outcomes in this group are therefore mainly based on retrospective studies from real world settings. Treatment with CPIs seems to be safe and effective also in patients with poor PS even though response rates and overall survival in this group is clearly inferior compared to patients with PS 0–1 16,31,32 . This observation is supported by our results indicating that PS as a single variable does not predict the development of IRAEs.…”

The 27-gene IO score is associated with efficacy of PD-1/L1 inhibitors independent of FGFR expression in a real-world metastatic urothelial carcinoma cohort

“…Multiple studies in bladder cancer have indicated that patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 have worse outcomes with ICI therapy than those with ECOG PS < 2 [34][35][36]. Prospective clinical trials with ECOG PS ≥ 2 are lacking, despite ICI therapy being an enticing option for the poor PS population.…”

The 27-gene IO score is associated with efficacy of PD-1/L1 inhibitors independent of FGFR expression in a real-world metastatic urothelial carcinoma cohort

“…Multiple studies in bladder cancer have indicated that patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 have worse outcomes with ICI therapy than those with ECOG PS < 2 (33)(34)(35). Prospective clinical trials with ECOG PS ≥ 2 are lacking, despite ICI therapy being an enticing option for the poor PS population.…”