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. 2021 Apr 12:11:666691.
doi: 10.3389/fonc.2021.666691. eCollection 2021.

Consolidation With Pembrolizumab and Nab-Paclitaxel After Induction Platinum-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer

Shetal A Patel  1 , David E Gerber  2 , Allison Deal  3 , Kathe Douglas  1 , Chad V Pecot  1 , Carrie Lee  1 , Joan Schiller  4 , Nirav Dhruva  5 , Jared Weiss  1
Affiliations

Consolidation With Pembrolizumab and Nab-Paclitaxel After Induction Platinum-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer

Shetal A Patel et al. Front Oncol. .

Abstract

Background: Induction with four cycles of platinum-based chemotherapy was the standard of care for metastatic non-small cell lung cancer (NSCLC) until the approval of immune checkpoint blockade (ICB) in the first-line setting. Switch maintenance therapy has shown promise in improving survival by exposing patients to novel, non-cross-resistant agents earlier in their treatment course.

Methods: We performed this open-label, three-arm, randomized phase II study (NCT02684461) to evaluate three sequences of consolidation with pembrolizumab and nab-paclitaxel in patients without progressive disease post induction chemotherapy. Consolidation was either sequential with pembrolizumab for four cycles followed by nab-paclitaxel for four cycles (P→A), nab-paclitaxel followed by pembrolizumab (A→P), or concurrent nab-paclitaxel and pembrolizumab for four cycles (AP).

Results: Twenty patients were randomized before the study was closed early due to the approval of first-line checkpoint inhibitors. We found that consolidation is feasible and well tolerated, with 30% of patients experiencing grade 3 toxicity. The median progression-free survival and OS in months (95% CI) in P→A were 10.1 (1.5-NR), 27.6 (1.7-NR); 8.4 (1.2-9.0), 12.7 (4.4-NR) in A→P; and 10.2 (5.1-NR), NR. Quality of life as measured by FACT-L improved in the majority of patients during the course of the study.

Conclusion: Sequential and concurrent consolidation regimens are well tolerated and have encouraging overall survival in patients with metastatic NSCLC.

Keywords: PD-1 antibody; fixed duration; immune checkpoint blockade; sequential therapy; switch maintenance.

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Conflict of interest statement

SP reports commercial research grants from Shattuck Labs and Dracen Pharmaceuticals. DG reports commercial research grants from AstraZeneca, Karyopharm, and BerGenBio, serving on a steering committee for Bristol-Myers-Squibb and is a paid consultant for Karyopharm, G1 Therapeutics, and Catalyst Therapeutics. CL is a paid consultant for Delcath Systems, Inc. JW reports commercial research grants from Merck and Celgene and has served as a paid consultant for Celgene. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study Schema.
Figure 2
Figure 2
Plots of Kaplan Meier Survival curves. (A) Progression-free survival (PFS). (B) Overall survival (OS) by arm.
Figure 3
Figure 3
Investigator assessed change in target lesions over time (*cutoff at 100%).
Figure 4
Figure 4
FACT-L scores. FACT-L score collected over the course of the study. Higher scores indicate improved quality of life.
Figure 5
Figure 5
Patient reported outcomes. A composite score was generated for each symptom. The maximum score for each patient across all three treatment arms over the course of the study is summarized in the graph below.
See this image and copyright information in PMC

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