Real-world immuno-oncology (IO) therapy treatment patterns and outcomes in patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) in the United States
Authors: X. Pan, M.M. Lin, Y. Yin, P. Hou, P. Baumann, M. Jahanzeb
Journal: Annals of Oncology (2019)

Background: Cancer immunotherapies are new treatment options in advanced NSCLC. Evidence of IO therapy efficacy in tumors with activating mutations, such as ALK rearrangements, is lacking. This retrospective study describes the characteristics of ALK+ NSCLC patients treated with IO therapy and assesses treatment outcomes (time to treatment discontinuation, real-world progression-free survival [rwPFS], overall survival [OS]). Methods: The Flatiron Health Electronic Health Record (EHR)−derived database (Jan 2011−Sep 2017) was used to identify patients with advanced ALK+ NSCLC who had received ≥1 ALK TKI and IO therapies (nivolumab, pembrolizumab, atezolizumab). Discontinuation of IO therapy was defined as switch to an ALK TKI or chemotherapy, death, or gap between last IO therapy administration and last follow-up date of > 120 days. rwPFS was estimated as the time from treatment initiation to progression (abstracted from clinician notes and radiology reports) or death. Time to discontinuation, rwPFS, and OS were analyzed using Kaplan-Meier methods. Results: Of 335 ALK+ NSCLC patients with follow-up between Jan 2015−Sep 2017, 32 (9.5%) patients were treated with IO therapy. Median age was 62.5 years, with 78.1% of patients diagnosed at stage IV, and 24 patients receiving nivolumab. Of the 32 IO treated patients, 15.6% received IO therapy before first ALK TKI, and 59.4% were treated with IO therapy after ≥2 ALK TKIs. Median (95% CI) time to discontinuation of IO therapy was 1.88 months (0.95 − 2.80), rwPFS was 2.17 months (1.18 − 2.93), and OS was 6.71 months (2.80−NE). Conclusions: We identified ALK+NSCLC patients who received IO therapy; most of whom were treated post ALK TKI. Time to discontinuation of IO therapy was short, and real-world effectiveness (rwPFS and OS) was limited. These results point to IO therapy's relative futility in ALK+ NSCLC patients. Compared to IO therapy, several approved ALK inhibitors have shown better effectiveness in both first and later lines of therapy. However, the optimal sequencing of ALK inhibitors with other therapies, including chemotherapy and IO therapy, remains unclear. Editorial acknowledgement: Jane Kondejewski, PhD of SNELL Medical Communication, Inc. Legal entity responsible for the study: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Funding: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Disclosure: M.M. Lin: Employer: Millennium Pharmaceuticals, Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company limited, which funded this study. X. Pan, Y. Yin, P. Hou, P. Baumann: Employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited which funded this study. M. Jahanzeb: Research Grant: Lilly, Boehringer Ingelheim, Callisto; Research Grant, consultant: Millennium/Takeda, Novartis, Ipsen, Roche/ Genentech, Pfizer.