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Purpose/objective(s): Clinical outcomes for limited stage small cell lung cancer (LS-SCLC) remain suboptimal. Standard of care chemoradiation with platinum/etoposide and thoracic radiation to 45 Gy delivered twice daily followed by prophylactic cranial irradiation yields a median overall survival of 30 months. LU005 is a randomized phase II/III trial designed to test the addition of atezolizumab to concurrent chemoradiation.Materials/methods: Patients with LS-SCLC (Tx-T4, N0-N3, M0) are randomly assigned in a 1:1 ratio to either standard chemoradiation, consisting of thoracic radiation (45 Gy twice daily or 66 Gy daily) with concurrent platinum/etoposide chemotherapy, or the experimental arm, consisting of the same chemoradiation regimen plus the addition of atezolizumab delivered concurrently with thoracic radiation, every 3 weeks for 12 months duration. Thoracic radiation begins with the second cycle of chemotherapy in both treatment arms. Stratification variables include radiation schedule (once daily vs. twice daily), chemotherapy (cisplatin vs. carboplatin), gender, and performance status (PS 0/1 vs. 2). Prophylactic cranial radiation is recommended for patients who have a response to treatment. The phase II primary endpoint is progression free survival (PFS) and the phase III primary endpoint is overall survival (OS). The overall sample size for phase II/III will be 506. Secondary endpoints include objective response rates, local control, distant metastases free, and quality of life. Correlative studies will include blood and tissue based tumor mutational burden analysis, with the hypothesis that higher mutational burden will predict for improved PFS in the experimental arm.Results: As of 3/01/2021, 374 sites are approved to enroll patients. Two-hundred patients have been accrued. Current enrollment is ahead of projected accrual.Conclusion: LU005 is a randomized II/III trial testing the addition of atezolizumab to standard chemoradiation for LS-SCLC. Accrual remains robust in spite of the ongoing COVID 19 pandemic.Funding: This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC) from the National Cancer Institute (NCI) and Genentech. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): We report mature outcomes of LSCLC patients randomized to the 61.2 Gy CB TRT arm of CALGB 30610/RTOG 0538. The study initially included 2 experimental arms, 61.2 Gy CB TRT over 5 weeks and 70 Gy daily (QD) over 7 weeks, both with higher predicted biologic efficacy than standard 45 Gy twice-daily (BID)TRT. The CB arm was discontinued after planned early interim analysis comparing toxicity in the experimental arms, but the study provides the largest prospective dataset assessing 61.2 Gy CB TRT in LSCLC MATERIALS/METHODS: Eligible patients had LSCLC with regional lymph node involvement, excluding contralateral hilar and supraclavicular nodes, and ECOG PS 0-2. TRT began with either the first or 2nd (of 4 total) cycle of cisplatin-based chemotherapy, and prophylactic cranial radiotherapy was recommended in cases of complete (or near complete) response. In the initial phase of the trial, patients were randomized with a 1:1:1 allocation to 45 Gy BID, 70 Gy QD and 61.2 Gy CB TRT. A decision to drop an experimental arm was mandated after toxicity data was available for approximately 70 patients in each cohort. Although toxicity was similar in both experimental arms, a decision was made to discontinue the 61.2 Gy cohort after discussion with the DSMB.Results: From March 2008 until March 2013 (when the cohort was discontinued), 93 patients were assigned to receive 61.2 Gy CB TRT. The median age was 62 years (range 41 to 77), the majority of patients were Caucasian (86%), male (51%), ECOG PS 0-1 (95%). Most patients started TRT with the first chemotherapy cycle (65%) and had 3D planning (63%). After median follow up of 7 years for surviving patients, median overall survival (OS) and progression free survival were 32.3 months (95% CI: 21.1-44.8) and 15.6 months (95% CI: 10.0-27.5), respectively. Two-year OS was 57% (95% CI: 0.47-0.68), with 28% OS (95% CI: 0.2-0.4) at 5 years. Rates of grade 3 and 4 hematologic adverse events (AEs) were 20.5% and 59.1%, with 40.9% and 25% Grade 3 and 4 non-hematologic AEs. Grade 3+ dysphagia and dyspnea were 16% and 7%, respectively. There were 4 Grade 5 AEs, including one patient with febrile neutropenia.Conclusion: Outcomes are similar to the contemporaneous CONVERT trial, and compare favorably to the prior phase II trial examining 61.2 Gy CB TRT (RTOG 0239) in LSCLC, despite the allowance of early stage (N0) disease in those studies. The improvement in OS compared with RTOG 0239 is likely attributed to improved staging and advances in radiotherapy planning and delivery, though additional factors may have contributed. Support: U10CA180821, U10CA180882; U10CA180868 (NRG), U10CA180888 (SWOG); https://acknowledgments.alliancefound.org Clinicaltrials.gov Id: NCT00632853. [ABSTRACT FROM AUTHOR]