OA09.03 Pembrolizumab in Combination With Platinum-Based Chemotherapy in Recurrent EGFR/ALK-Positive Non-Small Cell Lung Cancer (NSCLC)

Abstract

Efficacy of single-agent immune checkpoint inhibitors is limited in patients with EGFR/ALK-altered NSCLC. We conducted a phase II study to assess the efficacy of pembrolizumab in combination with carboplatin and pemetrexed in these patients. Patients with recurrent EGFR-mutated or ALK-rearranged NSCLC, previously treated with targeted therapy, were eligible. Patients were treated with carboplatin AUC5, pemetrexed 500 mg/m2 and pembrolizumab 200 mg I.V. every 3 weeks. After 4 cycles patients were maintained on pemetrexed and pembrolizumab for up to 2 years. Disease was assessed every 2 cycles for the first 6 cycles, then per investigator discretion. The primary end-point was RECIST 1.1 defined response rate. Secondary endpoints included PFS and OS. Tumor PD-L1 expression was assessed locally. Blood for circulating tumor cells (CTCs) was collected prior to the 1st and 3rd cycles. The plan was to enroll 28 evaluable patients in each of two separate cohorts of EGFR-mutated and ALK-rearranged NSCLC. Slow enrollment led to early termination of the trial. Of the 33 patients enrolled, 26 had EGFR-mutated NSCLC (13 del19, 9 L858R), 64% were female and median age was 67 years. The median number of prior treatments was 1 (range 1-3). 22 of 26 EGFR+ NSCLC patients had received prior osimertinib. Median number of cycles was 6 (2-24 cycles), with 4 patients, all EGFR+, still on therapy. Response rates (95%CI) were 42% (23%, 63%) and 29% (4%, 71%) among EGFR+ and ALK+ patients, respectively. Median duration of response was 6.1 months in all patients and in EGFR+ patients. Other efficacy results are provided below. Tumor PD-L1 expression was available for 30 patients and was ≥ 1% in 17. There was no difference in survival between patients with tumor PD-L1 <1% vs. ≥ 1%. The median CTC count at baseline in 15 EGFR+ patients in whom samples were available was 4/ml (0-23). Median overall survival among EGFR+ patients with decreased vs. increased CTC count during treatment was not reached vs. 18.5 months, respectively (p=0.52 for OS). The most common adverse events were fatigue, nausea, cytopenias, cough and dyspnea. The most common ≥ grade 3 toxicities were neutropenia, thrombocytopenia, thromboembolism, and AST/ALT elevation. One patient developed pneumonitis.TableEFGR+ (n=26)ALK+ (n=7)All (n=33)Median PFS (months. 95%CI)8.3 (7.2, 16.5)2.9 (1.1, NE)7.3 (5.3, 14.1)12-month PFS (95% CI)29% (14%, 59%)14% (2%, 88%)26% (13%, 50%)Median OS (months, 95% CI)22.2 (20.6, NE)2.9 (1.1, NE)20.6 (10.1, NE)12-month OS (95% CI)76% (59%, 97%)14% (2%, 88%)61% (44%, 83%) Open table in a new tab Pembrolizumab in combination with chemotherapy demonstrated a response rate of 42% and median survival of 22 months among patients with recurrent EGFR-mutated NSCLC. These results warrant further study of this combination in this patient population.