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A narrative review of toxicity of chemoradiation and immunotherapy for unresectable, locally advanced non-small cell lung cancer.

ABSTRACT: Despite declining smoking rates, lung cancer remains the second most common malignancy in the United States and the leading cause of cancer-related mortality. Non-small cell lung cancer (NSCLC) comprises roughly 85% of cases, and patients tend to present with advanced disease. Historically, concurrent chemoradiotherapy (CRT) has been the standard of care for stage III unresectable NSCLC but outcomes even with multimodal therapy have remained relatively poor. Efforts to improve outcomes through radiation dose escalation with conventional dose fractionation were unsuccessful with RTOG 0617, demonstrating significantly decreased overall survival (OS) with high dose radiation with respect to standard therapy. The recent PACIFIC trial established a new role for consolidative immune checkpoint blockade therapy after CRT using the programmed death ligand 1 (PD-L1) inhibitor durvalumab, by demonstrating significantly improved progression free survival and OS. Although promising, the addition of immunotherapy to multimodal therapy has generated debate regarding the most effective immune pathways to target, appropriate sequencing of therapy, most effective radiation techniques, and toxicity-related concerns. This review will highlight recent and ongoing trials in unresectable, locally advanced NSCLC that incorporate chemotherapy, radiation, and immunotherapy with an emphasis on analysis of treatment-related toxicities and implications for future study design.

SUBMITTER: Prasad RN

PROVIDER: S-EPMC7653152 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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A narrative review of toxicity of chemoradiation and immunotherapy for unresectable, locally advanced non-small cell lung cancer.

Prasad Rahul N RN Williams Terence M TM

Translational lung cancer research 20201001 5

Despite declining smoking rates, lung cancer remains the second most common malignancy in the United States and the leading cause of cancer-related mortality. Non-small cell lung cancer (NSCLC) comprises roughly 85% of cases, and patients tend to present with advanced disease. Historically, concurrent chemoradiotherapy (CRT) has been the standard of care for stage III unresectable NSCLC but outcomes even with multimodal therapy have remained relatively poor. Efforts to improve outcomes through r ...[more]

PMID: 33209624

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Project description:ImportanceAdministration of pembrolizumab plus concurrent chemoradiation therapy (cCRT) may provide treatment benefit to patients with locally advanced, stage III non-small cell lung cancer (NSCLC).ObjectiveTo evaluate treatment outcomes and safety of pembrolizumab plus cCRT in stage III NSCLC.Design, setting, and participantsThe phase 2, nonrandomized, 2-cohort, open-label KEYNOTE-799 study enrolled patients between November 5, 2018, and July 31, 2020, from 52 academic facilities and community-based institutions across 10 countries. As of October 28, 2020, median (range) follow-up was 18.5 (13.6-23.8) months in cohort A and 13.7 (2.9-23.5) months in cohort B. Of 301 patients screened, 216 eligible patients with previously untreated, unresectable, and pathologically/radiologically confirmed stage IIIA/IIIB/IIIC NSCLC with measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) were enrolled.InterventionsPatients in cohort A (squamous/nonsquamous) received 1 cycle (3 weeks) of carboplatin (area under the curve [AUC] 6 mg/mL/min), paclitaxel (200 mg/m2), and pembrolizumab (200 mg), followed by carboplatin (AUC 2 mg/mL/min) and paclitaxel (45 mg/m2) once weekly for 6 weeks and 2 cycles of pembrolizumab plus standard thoracic radiotherapy. Patients in cohort B (nonsquamous) received 3 cycles of cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and pembrolizumab (200 mg) every 3 weeks and thoracic radiotherapy in cycles 2 and 3. Patients received 14 additional cycles of pembrolizumab.Main outcomes and measuresCoprimary end points were objective response rate per RECIST v1.1 by blinded independent central review and incidence of grade 3 to 5 pneumonitis.ResultsA total of 112 patients received treatment in cohort A (76 men [67.9%]; median [range] age, 66.0 [46-90] years; 66 patients [58.9%] with programmed cell death ligand 1 [PD-L1] tumor proportion score ≥1%) and 102 patients received treatment in cohort B (62 men [60.8%]; median [range] age, 64.0 [35-81] years; 40 patients [39.2%] with PD-L1 tumor proportion score ≥1%). Objective response rate was 70.5% (79 of 112; 95% CI, 61.2%-78.8%) in cohort A and 70.6% (72 of 102; 95% CI, 60.7%-79.2%) in cohort B. Median duration of response was not reached, but 79.7% and 75.6%, respectively, had response duration of 12 months or longer. Grade 3 or higher pneumonitis occurred in 9 of 112 patients (8.0%) in cohort A and 7 of 102 (6.9%) in cohort B. Grade 3 to 5 treatment-related adverse events occurred in 72 of 112 (64.3%) and 51 of 102 (50.0%) patients, respectively.Conclusions and relevanceThe findings of this phase 2, nonrandomized, 2-cohort study suggest promising antitumor activity of pembrolizumab plus cCRT and manageable safety in patients with previously untreated, locally advanced, stage III NSCLC.

Dataset Information

A narrative review of toxicity of chemoradiation and immunotherapy for unresectable, locally advanced non-small cell lung cancer.

Publications

A narrative review of toxicity of chemoradiation and immunotherapy for unresectable, locally advanced non-small cell lung cancer.

Similar Datasets

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