Abstract
Background: Combination chemotherapy and immunotherapy regimens have significantly improved survival for patients with previously untreated advanced non–small cell lung cancer (NSCLC). Improvements in overall survival (OS) in two separate pembrolizumab trials have demonstrated survival improvements over chemotherapy alone, regardless of PD-L1 status. The optimal chemotherapy backbone for combina tion with immunotherapy is unknown. We hypothesized nab-paclitaxel may be a well-suited platinum partner to use in combination with check point inhibitor therapy for both adenocarcinoma and squamous histology and conducted a phase I/II trial to assess the efficacy of this regimen in advanced NSCLC. Methods: Adult patients with previously untreated, stage IIIB/IV NSCLC (any histology) with an Eastern Cooperative Oncology Group perfor mance status of 0-1, any PD-L1 expression, and no EGFR mutations or ALK translocations, received carboplatin area under the curve (AUC) 6 day 1, nab-paclitaxel 100 mg/m 2 days 1, 8, 15, and pembrolizumab 200 mg day 1 q21 days for 4 cycles followed by maintenance pembrolizumab q3w. Co-primary endpoints were progression-free survival (PFS) and overall response rate (ORR). Results: Forty-six evaluable patients enrolled, 14 in phase I and 32 in phase II, from June 2015 to July 2018 with a median duration of follow-up of 35.4 months. Median time from enrollment to data lock was 42 months. In the ITT population, the ORR was 35%, median PFS was 5.6 months (95% CI, 4.6-8.2), and median OS was 15.4 months (CI, 12.4-28.1). There were no statistical differences in PFS or OS by PD-L1 status. The 2- and 3-year landmark OS rates were 33% and 24%, respectively. Conclusion: Carboplatin, nab-paclitaxel, and pembrolizumab are a safe and effective regimen for patients with both squamous and nonsqua mous NSCLC. Although this study did not meet the prespecified endpoints, the median and landmark OS results are consistent with durable benefit of this regimen as seen in phase III trials for first-line treatment of advanced NSCLC. Key words: lung cancer; adenocarcinoma; carboplatin; nab-paclitaxel; pembrolizumab; immunotherapy Implications for Practice This phase I/II trial for patients with advanced non–small cell lung cancer (NSCLC) is the first trial to report a taxane-based regimen for use in all NSCLC histology subtypes in combination with pembrolizumab. Previous trials used a mix of either paclitaxel or nab-paclitaxel and restricted taxanes to patients with squamous histology. This study provides additional insights into the safety and tolerability of the nab-paclitaxel combination regimen used uniformly in all patients. Having these data in nonsquamous histology is important for clinical practice, particularly when the use of pemetrexed may be limited due to renal impairment. This study demonstrates long-term overall survival that compares favorably to historical controls and is comparable to long-term survival seen in contemporary phase III combination trials. Notably, this trial enrolled a higher proportion of African Americans, which is more representative of the general population than previously published in first-line immunotherapy trials for NSCLC. Received: 30 January 2023; Accepted: 25 May 2023. © The Author(s) 2023. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
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