A phase II study of pembrolizumab and paclitaxel in refractory extensive disease small cell lung cancer.

Abstract

8575 Background: Patients with platinum refractory extensive disease (ED) small cell lung cancer (SCLC) have a poor prognosis and a little progress have been made. We aimed to investigate the efficacy and safety of pembrolizumab and paclitaxel in these patients. Methods: In this phase II, open-label, multi-center study, 26 patients who progressed after etoposide/platinum chemotherapy were enrolled. The patients received paclitaxel 175mg/m2 every 3 weeks for up to 6 cycles. Pembrolizumab 200mg was added from the second cycle and continued until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS), safety, and biomarker analysis including programmed death-ligand 1 (PD-L1) expression, next-generation sequencing (NGS), and flow cytometric analysis of peripheral blood immune cells. Results: The median age was 68.5 years, and 88% were male. Of the 26 evaluable patients, the ORR was 23.1% (complete response: 3.8%, confirmed partial response [PR]: 19.2%, stable disease: 57.7%, progressive disease 7.7%, not evaluable 11.5%). Including unconfirmed PR, 38.4% responded, and disease control rate was 80.7%. The median PFS and OS were 5.0 months (95% CI, 2.7-6.7) and 9.2 months (95% CI, 6.6-15.1), respectively. Grade 3 or 4 adverse events included febrile neutropenia (8%), neutropenia (8%), asthenia (8%), hyponatremia (8%) and type I diabetes (4%). Four patients showed PD-L1 positivity and no significant difference in PFS was observed according to PD-L1 positivity (5.0 vs. 3.9 months, P= 0.897). NGS was performed in 12 tumor samples, and we could not find significant differences in mutational load or specific genetic alteration, except for the MET copy number gain (PFS 10.5 vs. 3.4 months, P= 0.019). According to flow cytometric analysis, NK cell activity was significantly lower in responders after 2 cycles of treatment (P= 0.022). Conclusions: Pembrolizumab and paclitaxel combination therapy showed a moderate activity with an acceptable toxicity in refractory ED SCLC. Further studies are warranted to define a subset of patients who may benefit from the addition of pembrolizumab. Clinical trial information: NCT02551432.