The second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib (Alcensa) topped chemotherapy in crizotinib-pretreated ALK+ non–small cell lung cancer (NSCLC), according to results from the phase 3 ALUR trial.
Median investigator-assessed progression-free survival was 9.6 months with alectinib and 1.4 months with chemotherapy (hazard ratio, 0.15; P less than .001), reported Silvia Novello, MD, PhD, of University of Turin (Italy) and her associates. Among patients with measurable central nervous system disease, the rate of CNS objective response was significantly higher for alectinib (54%) versus chemotherapy (0%; P less than .001), Dr. Novello and her associates reported in.
The multicenter, open-label ALUR trial was the first to directly compare alectinib with standard chemotherapy in patients with ALK-rearranged NSCLC that previously had been treated with both platinum-based chemotherapy and crizotinib. In all, 107 patients were randomly assigned on a 2:1 basis to receive either alectinib (600 mg twice daily) or chemotherapy (clinician’s choice of pemetrexed 500 mg/m2 or docetaxel 75 mg/m2 every 3 weeks).
A blinded independent review committee calculated median progression-free survival (PFS) times that were 2.5 months shorter for alectinib and 0.2 months longer for chemotherapy. Consequently, the hazard ratio for PFS was somewhat attenuated at 0.32 but remained highly significant (95% confidence interval, 0.17-0.59). “[Median] PFS with alectinib in ALUR has exceeded that observed with [second-line] ceritinib” during the ASCEND-5 study, the researchers wrote. In ASCEND-5, median independent review committee–assessed PFS time was 5.4 months, which is 1.7 months shorter than that for alectinib in ALUR. In each study, chemotherapy yielded a median PFS time of 1.6 months, which facilitated intertrial comparisons, they wrote.
Rates of all-grade and serious adverse events were similar between arms in ALUR. Alectinib therapy caused no fatal adverse events, while chemotherapy was associated with one fatality deemed unrelated to treatment. Alectinib was more likely to produce constipation, dyspnea, and hyperbilirubinemia, while chemotherapy was more likely to cause nausea, alopecia, neutropenia, diarrhea, pruritus, stomatitis, and bacterial pneumonia. Although patients stayed on alectinib a median of 14 weeks longer than on chemotherapy, they were less likely to stop alectinib (6%) than chemotherapy (9%) for adverse events.
Dr. Novello disclosed personal fees from Roche, which markets alectinib. Eleven coinvestigators also disclosed employment, stock ownership, or other financial ties to Roche.
SOURCE: Novello S et al. Ann Oncol. 2018 Apr 14.