The current standard of care for fit patients with unresectable stage III NSCLC involves concurrent chemoradiation (CRT) followed by durvalumab. Disease recurrence occurs in approximately 2/3 of patients, often necessitating subsequent systemic therapy. The only available data about re-challenge immune checkpoint blockers (ICB) in this setting derives from small retrospective series. We evaluated progression free survival (PFS) and overall survival (OS) in patients receiving either ICB-based therapy versus a chemotherapy (CT)-only for disease progression after CRT and durvalumab. Multicenter retrospective study, conducted across 10 centers in Italy, the USA, Israel, and The Netherlands. Consecutive patients with relapsed NSCLC following CRT and durvalumab were enrolled. A total of 197 patients met the eligibility criteria: 93 received CT ( ± anti-VEGF), and 104 received an ICB-based treatment ( ± CT). The median PFS for patients receiving an ICB-based versus a CT-only regimen was 5.9 (95 % CI 4.3-7.6) versus 4.9 months (95 % CI 3.9-5.8), respectively (p = 0.011, HR: 0.67, 95 % CI 0.49-0.91). The median OS was 14.6 months (95 % CI 9.9-19.4) versus 8.9 (95 % CI 7.4-10.4), respectively (p = 0.005, HR: 0.61, 95 % CI 0.43-0.86). Patients with PFS ≥ 12 months on durvalumab, treated with subsequent ICB or CT median OS was 22.0 (95 % CI: 12.9-31.2) 9.8 months (95 % CI: 4.3-15.2) respectively (p = 0.024). Among patients with a PFS < 12 months on durvalumab there was no significant OS difference between ICB and CT arms. ICB retreatment at disease progression after CRT and durvalumab might offer an OS benefit over CT in patients who do not relapse during durvalumab treatment.

Purpose: Disparities in cancer care delivery remain a pressing health-care crisis within the United States (US). The use of immune checkpoint inhibitors (ICIs) and their management may be a disparity generator that impacts survival. This retrospective study assessed disparities in a cohort of patients with a variety of solid tumors treated with ICIs within a single health-care organization focusing on the impact of race, socioeconomic status (SES) and site of care delivery on survival and the development of severe immune-related adverse events (irAEs). Patients and Methods: Manual chart review was performed on all patients with solid tumors treated with ICIs within a health-care organization from 2012 to 2018. Care delivery was dichotomized as DOP (disease-oriented provider at academic center) and COP (community oncology provider). Primary and secondary outcomes were overall survival (OS) and rates of grade 3– 4 irAEs, respectively. Relationships with covariates of interest, including race, socioeconomic status and type of care delivery, were assessed among both outcomes. Results: A total of 1070 eligible patients were identified. Of those, 11.4% were of Black race, 59.7% had either non-small cell lung cancer (NSCLC) or melanoma and 82.8% had stage IV disease. Patients of Black race and lower SES were more likely to be treated by DOPs (p< 0.0001). A superior OS was associated with care delivered by DOPs when compared to COPs (HR 0.68; 95% CI 0.56– 0.84; p=0.0002), which was durable after accounting for race, SES, histopathologic diagnosis and disease stage. Melanoma patients experienced higher rates of severe irAEs (HR 2.37; 95% CI 1.42– 3.97; p=0.001). Race, SES and site of care delivery were not related to rates of severe irAEs. Conclusion: In a large health-care organization, patients treated with checkpoint inhibitors by DOPs benefited from a significant OS advantage that was durable after controlling for racial and socioeconomic factors, providing evidence that disease-oriented care has the potential to mitigate racial and socioeconomic disparities.

Operable non-small cell lung cancer (NSCLC) has been traditionally managed with surgical resection, often followed by adjuvant chemotherapy with or without radiotherapy. However, disease recurrence still occurs approximately 50% of the time. Most recently, (neo) adjuvant/perioperative systemic therapy has evolved to include checkpoint inhibitor therapy and targeted therapies that have proved successful in advanced disease settings. We provide a comprehensive review of the trials investigating neoadjuvant, adjuvant, and perioperative systemic therapies in resectable lung cancer, including a discussion on surrogate survival endpoints. We review the management of N2 disease, the utility of circulating tumor DNA (ctDNA) in determining the risk and benefit from systemic therapy in operable NSCLC, as well as future directions of investigation.

Introduction: Liquid and tissue next-generation sequencing (NGS) are both important in oncological care. We report a case of metastatic non-small cell lung adenocarcinoma (NSCLC) with a rare epidermal growth factor receptor kinase domain duplication (EGFR-KDD) identified on liquid biomarker testing which led to sustained targeted treatment. Case Presentation: A 54-year-old male was diagnosed with metastatic NSCLC and progressed on multiple lines of therapies: carboplatin-pemetrexed-pembrolizumab, cisplatin-docetaxel, and durvalumab-tremelimumab over a 6-month period. Liquid NGS identified a rare EGFR-KDD mutation that was treated with osimertinib leading to 5 months of progression-free survival and significant clinical improvement before ultimately opting for hospice due to intolerance with osimertinib. Conclusion: Liquid and tissue NGS should be used in combination to guide treatment and monitor treatment response. Osimertinib may be particularly effective in metastatic NSCLC with EGFR-KDD mutations.