Prospective Phase II Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy (SBRT) Followed By Concurrent Mediastinal Chemoradiation and Adjuvant Immunotherapy for Locally-Advanced Non-Small Cell Lung Cancer (LA NSCLC)

Purpose/Objective(s)To report the efficacy and toxicity outcomes of a prospective phase II trial of primary tumor SBRT followed by conventional chemoradiation to the lymph nodes and adjuvant immunotherapy in patients (pts) with unresectable LA NSCLC.Materials/MethodsEligible pts included stage II-III LA NSCLC with peripheral primary tumors ≤ 7cm or centrally based tumors that had at least 2 cm separation from involved nodal disease. Pts received SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by standard radiation to 60 Gy in 30 fractions to the involved lymph nodes with concurrent platinum doublet chemotherapy. The trial was amended to allow pts without disease progression after chemoradiation to receive adjuvant durvalumab per the PACIFIC trial. The primary endpoint was 1 year progression free survival (PFS), evaluated as a binary variable. Frequencies and proportions were used for reporting this primary endpoint, in addition to adverse events and patterns of failure. Median PFS and OS were estimated using Kaplan Meier methods.ResultsSafety and efficacy is reported on the first 50 pts enrolled in the trial with a median follow-up of 24 months (mos) (range, 1-54 mos). Pts were primarily stage IIIA (60%) or stage IIIB (34%), with 6% of pts stage IIB. Overall grade 3 or higher toxicity related to SBRT and/or mediastinal radiation was 8% with two pts (4%) developing grade 3 pneumonitis and one pt having a grade 5 lung infection possibly related to radiation. Overall grade 2 pneumonitis related to SBRT or mediastinal radiation was 20%. Only one pt (2%) developed grade 3 esophagitis. No late cardiac events have been observed. The one-year PFS for all pts was 62% with a median PFS of 26.3 mos and median overall survival of 40.8 mos. Of the 50 pts enrolled, 37 received at least one dose of adjuvant durvalumab. The one-year PFS for pts who received at least one dose of durvalumab was 70.3% with a median PFS not yet reached in this group (median follow-up 24 mos). Patterns of failure were mostly distant with 26% of pts experiencing distant failure, 6% regional, and 2% distant and regional. There was only one local failure (2%) after SBRT in all 50 pts.ConclusionSBRT to the primary tumor followed by conventional chemoradiation to the involved lymph nodes and adjuvant immunotherapy was well tolerated and showed improved 1-year PFS compared to prior conventional chemoradiation trials for locally advanced NSCLC. The results of this trial will be further evaluated in a randomized phase III study, NRG LU-008. Pts will receive either conventional chemoradiation vs. SBRT to the primary tumor followed by chemoradiation to the involved lymph nodes followed by consolidative immunotherapy to evaluate the possibility of utilization of SBRT as a new standard of care for LA NSCLC. To report the efficacy and toxicity outcomes of a prospective phase II trial of primary tumor SBRT followed by conventional chemoradiation to the lymph nodes and adjuvant immunotherapy in patients (pts) with unresectable LA NSCLC. Eligible pts included stage II-III LA NSCLC with peripheral primary tumors ≤ 7cm or centrally based tumors that had at least 2 cm separation from involved nodal disease. Pts received SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by standard radiation to 60 Gy in 30 fractions to the involved lymph nodes with concurrent platinum doublet chemotherapy. The trial was amended to allow pts without disease progression after chemoradiation to receive adjuvant durvalumab per the PACIFIC trial. The primary endpoint was 1 year progression free survival (PFS), evaluated as a binary variable. Frequencies and proportions were used for reporting this primary endpoint, in addition to adverse events and patterns of failure. Median PFS and OS were estimated using Kaplan Meier methods. Safety and efficacy is reported on the first 50 pts enrolled in the trial with a median follow-up of 24 months (mos) (range, 1-54 mos). Pts were primarily stage IIIA (60%) or stage IIIB (34%), with 6% of pts stage IIB. Overall grade 3 or higher toxicity related to SBRT and/or mediastinal radiation was 8% with two pts (4%) developing grade 3 pneumonitis and one pt having a grade 5 lung infection possibly related to radiation. Overall grade 2 pneumonitis related to SBRT or mediastinal radiation was 20%. Only one pt (2%) developed grade 3 esophagitis. No late cardiac events have been observed. The one-year PFS for all pts was 62% with a median PFS of 26.3 mos and median overall survival of 40.8 mos. Of the 50 pts enrolled, 37 received at least one dose of adjuvant durvalumab. The one-year PFS for pts who received at least one dose of durvalumab was 70.3% with a median PFS not yet reached in this group (median follow-up 24 mos). Patterns of failure were mostly distant with 26% of pts experiencing distant failure, 6% regional, and 2% distant and regional. There was only one local failure (2%) after SBRT in all 50 pts. SBRT to the primary tumor followed by conventional chemoradiation to the involved lymph nodes and adjuvant immunotherapy was well tolerated and showed improved 1-year PFS compared to prior conventional chemoradiation trials for locally advanced NSCLC. The results of this trial will be further evaluated in a randomized phase III study, NRG LU-008. Pts will receive either conventional chemoradiation vs. SBRT to the primary tumor followed by chemoradiation to the involved lymph nodes followed by consolidative immunotherapy to evaluate the possibility of utilization of SBRT as a new standard of care for LA NSCLC.