Discussion
non-small cell lung cancer, AML
NON-SMALL CELL LUNG CANCER, INTERSTITIAL LUNG DISEASE, RECRUITMENT, AML
Treatment of AML in elderly patients ineligible for intensive chemotherapy remains a significant challenge. This randomized, double-blind, placebo-controlled phase 2 trial was conducted to evaluate the efficacy and safety of nintedanib, a small molecule triple angiokinase inhibitor, in combination with LDAC in older patients with AML who were considered ineligible for intensive chemotherapy. The results of the dose-finding phase 1 part of the study had been published before and suggested a continuation of the trial with a phase 2 recommended dose (P2RD) of 200 mg nintedanib twice daily in combination with LDAC [The study was stopped prematurely with approximately one-third of the patient number initially planned. Reasons for slow recruitment might have been competing trials in an identical patient cohort and increasing availabilities of alternative treatment options (e.g., venetoclax-based therapies).While nintedanib plus LDAC continued to present a well manageable safety profile, the addition of nintedanib to LDAC was not associated with a superior OS compared to placebo and LDAC. Likewise, no signals for a beneficial effect of adding nintedanib were observed in the subgroup of patients who entered the study with r/r AML, whereas no conclusion could be made for the group of patients with previously untreated AML, due to low numbers. Response rates, time on treatment, 30-day mortality, and number of patients reaching maintenance therapy were also similar in both arms. Overall, the outcome in our study was comparable to outcomes reported in larger trials using LDAC monotherapy as a comparator [This disappointing result is in line with previous observations on the lack of efficacy of other anti-angiogenic drugs in AML, such as the VEGF antibody bevacizumab when given alone [In conclusion, the triple angiokinase inhibitor nintedanib, approved for the treatment of advanced non-small cell lung cancer and fibrotic interstitial lung disease, had a manageable safety profile consistent with prior data, but showed no superior therapeutic activity over placebo when added to LDAC in elderly AML patients considered unfit for intensive chemotherapy.