Immunotherapy After Chemotherapy and Radiation for Clinical Stage III Lung Cancer

Abstract

IMPORTANCEThe 2017 international PACIFIC trial established a role for immunotherapy after chemoradiation for unresectable stage III non-small cell lung cancer (NSCLC). However, in the US, patients with NSCLC commonly differ from clinical trial populations in terms of age, health, access to care, and treatment course, which may all factor into the efficacy of immunotherapy. OBJECTIVETo determine the outcomes of immunotherapy use in unresectable stage III NSCLC in the general US population. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed the National Cancer Database for patients diagnosed with clinical stage III NSCLC between 2015 and 2017 with follow-up through the end of 2018 who were treated with chemotherapy and radiation. Data were analyzed January 2022. MAIN OUTCOMES AND MEASURES Mortality hazard in a multivariable Cox proportional hazards model and survival among a propensity-matched sample treated with chemotherapy and radiation, with and without immunotherapy. RESULTS A total of 23 811 patients with clinical stage III NSCLC with median (IQR) age 66 (59-72) years met inclusion criteria (10 454 [43.9%] women; 564 [2.4%] Asian, 2930 [12.3%] Black, 20 077 [84.3%] White patients), including 209 (16.1%) patients with multiple comorbidities and 1297 (5.4%)immunotherapy recipients. Immunotherapy after chemotherapy and radiation was associated with reduced mortality (hazard ratio [HR], 0.74; 95% CI, 0.67-0.82; P < .001). Among a propensitymatched sample, immunotherapy was associated with superior 3-year survival (52% [1297 patients at 0 months, 56 patients at 36 months] vs 44% [2594 patients at 0 months, 173 patients at 36 months]; P < .001). The treatment of 833 patients who received immunotherapy (64.2%) differed from the PACIFIC trial protocol, including 221 patients (17.0%) who received radiation doses outside of the protocol range and 731 patients (56.4%) who started immunotherapy more than 6 weeks after radiation was completed. The survival advantage of immunotherapy persisted when initiated up to 12 weeks after radiation was completed (HR, 0.75; 95% CI, 0.61-0.92). Among patients who received radiation outside the PACIFIC protocol range, the survival advantage of immunotherapy was not significant (HR, 0.87; 95% CI, 0.69-1.01). CONCLUSIONS AND RELEVANCEIn this cohort study, immunotherapy after chemotherapy and radiation for stage III NSCLC was associated with a survival advantage in the general US population despite two-thirds of patients treated differently than the PACIFIC protocol. The findings suggest there may be flexibility in the timing of immunotherapy initiation after radiation; further study is warranted to clarify the clinical benefits of immunotherapy.

Multiomic-Based Molecular Landscape of FaDu Xenograft Tumors in Mice after a Combinatorial Treatment with Radiation and an HSP90 Inhibitor Identifies Adaptation-Induced Targets of Resistance and Therapeutic Intervention

“…Using radiation to make tumors susceptible to drugs that did not work before treatment may provide a highly impactful new role for radiation as we have observed in vitro ( 10, 22, 34, 38 ). Radiation priming strategies are being studied in close proximity to immunotherapy ( 46, 47 ). The short-term data in this experiment and our long-term in vitro data indicate immunologic adaptation which may provide additional opportunities for immunotherapy.…”

A Review of the Current Approach and Treatment Landscape for Stage III Non-Small Cell Lung Cancer

“…PACIFIC trial data showed a significant improvement in progression-free survival (PFS) and overall survival (OS) with durvalumab in patients with inoperable stage III disease treated with concurrent chemoradiation [15]. A real-world study also showed that consolidation with immunotherapy led to better survival even in patients treated outside the PACIFIC trial protocol [16]. In this article, we provide an overview of the treatment of stage III NSCLC, particularly focusing on the recent advancements in the last 5 years.…”