Treatment with PD-1 inhibitors in NSCLC beyond disease progression: Impact on symptoms and cost.

Abstract

174 Background: Immunotherapy with PD-1 axis inhibitors has become standard of care in the treatment of patients with advanced non-small cell lung cancer (NSCLC), with improved survival and less toxicity than chemotherapy. Response patterns to PD-1 axis inhibitors can be unconventional, including pseudoprogression. Identifying disease progression using RECIST has been challenging. We explored treatment past progression (TPP) with PD-1 inhibitors and its impact on patient symptoms and costs. Methods: Retrospective analysis of consecutive patients with advanced NSCLC that received single agent PD-1 inhibitors at the Princess Margaret Cancer Centre (PMH) between 2013 and 2017. Patient symptom burden was assessed by Edmonton Symptom Assessment Scale (ESAS) at outpatient clinic visits. Drug acquisition costs were calculated using hospital-based costs for the agents used and both actual and fixed dosing recommendations. Results: The study cohort included 89 patients with advanced NSCLC. Median age was 62, half were female and 75% had adenocarcinoma. Most, 70%, developed disease progression during treatment, 19% stopped due to toxicity. Twenty-one patients received TPP (23% of entire cohort, 34% of those with progression). Demographic characteristics except age and baseline symptom scores were similar between groups. Younger patients (p = 0.046), those with lower symptom burden upon RECIST progression (mean ESAS 14.7 vs. 27.2 non-TPP, p = 0.013) and greater symptom improvement from baseline (mean ESAS change -11.7 vs. -2.3 non-TPP, p = 0.11) were more likely to receive TPP. During TPP, only 1 patient achieved tumor response. TPP represented 29% of total treatment costs. This did not vary significantly between weight- based and fixed dosing. However, the costs of treatment of the entire cohort was 23% higher using fixed dosing compared to weight-based. Conclusions: : Treatment with immunotherapy beyond RECIST progression is common in advanced lung cancer, although patient benefit is rare. This can lead to substantial expenditure without clear value for most patients. Better methods for detecting early failure of immunotherapy in advanced NSCLC are needed, to allow patients to switch to more active treatment.