The population-based effects of the FDA’s approval of durvalumab as consolidative therapy in patients with locally-advanced non-small cell lung cancer.
Authors: Kemnasom Nwanwene, Rick Voland, John Charles Flickinger, Malcolm DeCamp, Nepal Chowdhury, Juan Bastidas, Toni Pacioles, Mina Shenouda, Muhammad Jamil, Maria Tria Tirona, Yousef Shweihat, John Varlotto
Journal: Journal of Clinical Oncology (2024)

e20086 Background: In 2018, consolidative durvalumab (D) was FDA-approved in patients with locally advanced non-small cell lung cancer(NSCLC) because it increased PFS and was later found to increase overall survival (OS). This analysis will check the real-world effects of this agent prior to and after its approval. Methods: The SEER-17 database was queried from 2015-2020 and assessed for differences in OS/lung cancer specific survival (LCSS) and rates of second cancers (2C). Patients included were those with NSCLC who received chemotherapy and radiation with at least 7 months of follow-up. The population was split into two different groups, those diagnosed before and after D’s approval (2015-2017(BA) and 2018-2020(AA). Multi-variate analyses (MVA) were used to find prognostic factors which were used to adjust OS/LCSS rates for the BA and AA at 12, 24, and 30 months. Variables analyzed included patient characteristics, histopathology, and previous cancers (separated into alcohol, diet, smoking, virus and hormone related). Inverse propensity scores were weighted for OS factors to determine rates of second cancers. Results: Of 12,022 patients, 501 patients developed 2Cs. The OS was significantly better for AA group than the BA group ( p &lt; 0.001, HR = 0.79(0.74, 0.85) with rates at 12, 24, and 30 months of 0.86, 0.68, and 0.62%; and 0.83, 0.62, and 0.55%. Multivariate analyses for OS demonstrated similar prognostic factors in both year groups and were worse with advanced age, male sex, unmarried status, squamous histology, advanced stage and non-Hispanic white race. The LCSS was significantly better in AP than the BA group ( p &lt; 0.001, HR = 0.84 (0.7, 0.89) with rates at 12, 24, and 30 months of groups of 0.82,0.61, and 0.55%; and 0.80,0.56,and 0.48%. The prognostic factors for LCSS were the same in both group and included age, male sex, squamous histology, and advanced stage. The adjusted rates of 2C in 2018-2020 group were trending less than in 2015-2017 (HR = 0.80(0.63-1.03), p =0.07), largely driven by a reduction in smoking-related cancers (HR = 0.74(0.53-1.02, p= 0.07). The 2C rates at 12, 24, and 30 months were 1.0, 2.7, and 3.5% in the 2015-2017 and 0.9, 1.6, and 1.9% in 2018-2020 groups. MVA significant risk factors for 2Cs were age, history of previous cancer, male sex, and squamous histology in the BA group, but no factors were significant for 102 second cancers in the AA group. Conclusions: In the years after durvalumab's approval, there was a significant benefit in terms of overall survival and lung cancer specific survival, but prognostic factors remained similar. In addition to the OS/LCSS benefit, durvalumab's approval was associated with a strong trend for reducing the incidence of second cancers, especially in those with previous smoking related cancers.