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OBJECTIVE: The objective of this article is to review the efficacy, safety, and evidence for current use and potential future uses of immune-checkpoint inhibitors (ICIs) in the management of resectable non-small cell lung cancer (NSCLC). DATA SOURCES: A literature review was carried out through PubMed to identify completed and ongoing clinical trials evaluating the use, efficacy, and safety of ICIs in the management of resectable NSCLC. DATA SUMMARY: To date, four phase 3 trials have emerged that have changed our treatment practice concerning the utilization of ICIs during the adjuvant and neoadjuvant settings. The IMpower010 and KEYNOTE-091 trials examined the application of adjuvant atezolizumab and pembrolizumab, respectively, following surgical resection and adjuvant chemotherapy. In the CheckMate 816 trial, the combination of nivolumab and chemotherapy as a neoadjuvant therapy received approval for patients with resectable NSCLC. Also, for patients with resectable NSCLC, the use of a pembrolizumab and chemotherapy combination as a perioperative therapy received approval based on the results of the KEYNOTE-671 trial. Apart from these trials, there are numerous phase 2 and phase 3 trials, some of which have been published while others are still in progress. CONCLUSION: Despite the promising outcomes from these trials there remain several unanswered questions. In this review, we will assess clinical trials involving adjuvant, neoadjuvant, and perioperative ICIs, aiming to address the unresolved questions related to these therapeutic approaches.
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PURPOSE: Phase 3 studies of intravenous amivantamab demonstrated efficacy across EGFR-mutated advanced non-small cell lung cancer (NSCLC). A subcutaneous formulation could improve tolerability and reduce administration time while maintaining efficacy. PATIENTS AND METHODS: Patients with EGFR-mutated advanced NSCLC who progressed following osimertinib and platinum-based chemotherapy were randomized 1:1 to receive subcutaneous or intravenous amivantamab, both combined with lazertinib. Co-primary pharmacokinetic noninferiority endpoints were trough concentrations (Ctrough; on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUCD1-D15). Key secondary endpoints were objective response rate (ORR) and progression-free survival (PFS). Overall survival (OS) was a predefined exploratory endpoint. RESULTS: Overall, 418 patients underwent randomization (subcutaneous group, n=206; intravenous group, n=212). Geometric mean ratios of Ctrough for subcutaneous to intravenous amivantamab were 1.15 (90% CI, 1.04-1.26) at cycle-2-day-1 and 1.42 (90% CI, 1.27-1.61) at cycle-4-day-1; the cycle-2 AUCD1-D15 was 1.03 (90% CI, 0.98-1.09). ORR was 30% in the subcutaneous and 33% in the intravenous group; median PFS was 6.1 and 4.3 months, respectively. OS was significantly longer in the subcutaneous versus intravenous group (hazard ratio for death, 0.62; 95% CI, 0.42-0.92; nominal P=0.02). Fewer patients in the subcutaneous group experienced infusion-related reactions (13% versus 66%) and venous thromboembolism (9% versus 14%) versus the intravenous group. Median administration time for first infusion was reduced to 4.8 minutes (range, 0-18) for subcutaneous amivantamab from 5 hours (range, 0.2-9.9) for intravenous amivantamab. During cycle-1-day-1, 85% and 52% of patients in the subcutaneous and intravenous groups, respectively, considered treatment convenient; end-of-treatment rates were 85% and 35%, respectively. CONCLUSION: Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced infusion-related reactions, increased convenience, and prolonged survival.