AUTHOR=Goldman Jonathan W. , Waterhouse David M. , George Ben , O'Dwyer Peter J. , Bhore Rafia , Banerjee Sibabrata , Lyons Larry , Louis Chrystal U. , Ong Teng Jin , Kelly Karen 

TITLE=Safety and Efficacy Results of a Phase I, Open-Label Study of Concurrent and Delayed Nivolumab in Combination With nab-Paclitaxel and Carboplatin in Advanced Non-small Cell Lung Cancer

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01256

DOI=10.3389/fonc.2019.01256

ISSN=2234-943X

ABSTRACT=<p><bold>Introduction:</bold> Multicenter, phase I study of concurrent and delayed nivolumab plus <italic>nab</italic>-paclitaxel/carboplatin in advanced non-small cell lung cancer (NSCLC).</p><p><bold>Methods:</bold> Chemotherapy-naive patients with advanced NSCLC (ineligible for potentially curative radiation or surgery) received <italic>nab</italic>-paclitaxel 100 mg/m<sup>2</sup> (days 1, 8, 15) and carboplatin area under the curve 6 (day 1) intravenously every 21 days (first 4 cycles); nivolumab 5 mg/kg was administered intravenously (day 15) beginning in cycle 1 (concurrent) or cycle 3 (delayed) in separate cohorts and continued beyond the 4 chemotherapy cycles. The primary objective was to assess safety. Secondary objectives were to assess tolerability and explore antitumor activity.</p><p><bold>Results:</bold> All 32 patients received chemotherapy; 20 of 22 and 6 of 10 patients also received concurrent or delayed nivolumab, respectively. No dose-limiting toxicities were reported in the concurrent cohort; 1 dose-limiting toxicity was reported in the delayed cohort. In the concurrent cohort, 20 patients (91%) had ≥1 grade 3/4 treatment-emergent adverse event (TEAE), and 7 (32%) discontinued treatment due to TEAEs. In the delayed cohort, all patients had ≥1 grade 3/4 TEAE, and 2 (20%) discontinued due to TEAEs. The median progression-free and overall survival, respectively, were 10.5 and 29.3 months in the concurrent cohort and 4.1 and 8.2 months in the delayed cohort.</p><p><bold>Conclusions:</bold> The safety profile of the combination was consistent with that of individual agents and generally similar in the 2 cohorts. Efficacy outcomes in the concurrent cohort, but not in the delayed cohort, were encouraging and support the rationale for concurrent administration of nivolumab with <italic>nab</italic>-paclitaxel/carboplatin for the treatment of advanced NSCLC.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.ClinicalTrials.gov</ext-link>, identifier: NCT02309177</p>