P2.03a-049 Response to Salvage Chemotherapy Following Exposure to PD-1 Inhibitors in Patients with Non-Small Cell Lung Cancer: Topic: Clinical Trials

Abstract

Programmed death-1 (PD-1) inhibitors are effective second line treatment in non-small cell lung cancer (NSCLC), however objective responses are seen in only 20-30% of patients. While a minority of patients achieve durable response to PD-1 inhibitors, those who progress or are refractory receive salvage chemotherapy. We evaluate response to salvage chemotherapy following exposure to PD-1 inhibitors. Eligible patients were adults with NSCLC followed at the Vanderbilt Cancer Center or the Winship Cancer Institute from 2011 to 2016 who received salvage chemotherapy following PD-1 inhibitors (cases) versus no PD-1 inhibitors (controls). CT-imaging of the chest/abdomen/pelvis was done within 4 weeks of initiation of salvage chemotherapy and every 6 weeks thereafter. Revised RECIST guidelines were used to define response to treatment. Clinical and imaging data were abstracted from review of electronic medical records. Multivariate logistic regression analysis was used to calculate probability of response. Three hundred patients’ charts were reviewed and 56 patients met eligibility criteria. Among evaluable patients, 28 were males versus 28 females. Median age was 61.64 years (interquartile ranges (IQR): 55.33–69.36) in cases versus 67.82 (IQR: 54.08-72.24) in controls. Forty-one patients were classified as cases versus 15 controls. Thirty-six patients received nivolumab and 5 pembrolizumab. Forty-five (80%) patients had adenocarcinoma, 10 (18%) squamous cell carcinoma and 1 (2%) large cell carcinoma. The median number of chemotherapy regimens prior to salvage chemotherapy was 3 (IQR: 2-3) in cases versus 2 (IQR: 1-2) in control. The drugs most commonly used in salvage regimens included docetaxel, pemetrexed, paclitaxel, gemcitabine. Seven (17%) cases had partial response to chemotherapy versus 1 (6.6%) controls. Eleven (27%) cases had progressive disease versus 6 (40%) controls. Twenty-three (56%) cases had stable disease versus 8 (53%) controls. The odd ratio for achieving a partial response was 0.16 (95% CI: 0.08 to 0.35, P=0.000). In multiple logistic regression model, age, gender, number of prior chemotherapy regimens, tumor histology, smoking status, different salvage chemotherapy regimens were not associated with the likelihood of achieving a partial response. The odds of achieving a partial response to salvage chemotherapy were 6 times higher in patients with prior exposure to PD-1 inhibitors. This observed difference however warrants confirmation in larger cohorts. If confirmed, this difference may represent an argument to promote immune PD-1 inhibitors as first line regimen for the treatment of NSCLC not amenable to targeted therapy.