medwireNews: The findings of the ALUR trial and of an additional analysis of the ALEX trial confirm the benefits of treatment with the second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib in patients with advanced ALK-positive non-small-cell lung cancer (NSCLC).
Both sets of results were presented at the ESMO 2017 Congress, held in Madrid, Spain.
The phase III ALUR trial pitted alectinib against chemotherapy in patients who had progressed after treatment with platinum-based chemotherapy and the first-generation ALK inhibitor crizotinib, and showed a significant progression-free survival (PFS) gain with alectinib.
Specifically, investigator-assessed PFS was a median of 9.6 months for the 72 patients randomly assigned to receive alectinib 600 mg twice daily and 1.4 months for the 35 patients given pemetrexed or docetaxel, a significant difference equating to a hazard ratio (HR) of 0.15.
The findings were similar when PFS was assessed by an independent review committee, with corresponding median PFS times of 7.1 and 1.6 months, and a significant HR of 0.32.
Of note, just over half (54.2%) of the 24 alectinib-treated patients with baseline central nervous system (CNS) metastases achieved an objective response, whereas as none of the 16 patients in the chemotherapy group had a CNS response.
Alectinib also had a more favorable safety profile, said presenting author Silvia Novello (University of Turin, Italy), with adverse events of grade 3 or 4 occurring in 27.1% of patients given alectinib and 41.2% of those given chemotherapy. Fewer patients in the alectinib than chemotherapy arm needed a dose reduction (4.3 vs 11.8%) or discontinued treatment (5.7 vs 8.8%), but alectinib-treated patients were more likely to have a dose interruption (18.6 vs 8.8%).
Novello concluded that these findings “confirm the previously proven benefit of alectinib” in this patient population.
The CNS efficacy results of the ALEX trial, presented by Shirish Gadgeel, from the University of Michigan in Ann Arbor, USA, also add to the evidence base for alectinib.
In the phase III trial, 152 patients with previously untreated, ALK-positive, stage IIIB or IV NSCLC were randomly assigned to receive alectinib 600 mg twice daily, while their 151 counterparts received crizotinib 250 mg/day. Sixty-four patients in the alectinib group and 58 in the crizotinib group had CNS metastases at baseline.
Median PFS was significantly longer with alectinib than with crizotinib among patients with baseline CNS disease, at not reached versus 7.4 months (HR=0.40), and also among those free of CNS metastases at intake, at not reached versus 14.8 months (HR=0.51).
Gadgeel also reported the results of a competing risks analysis, which showed that the 1-year cumulative incidence of CNS progression as a first event was lower with alectinib than crizotinib, with rates of 16.0% versus 58.3% for patients with baseline CNS metastases and 4.6% versus 31.5% for those without, the latter finding suggesting that “alectinib is protective against the development of CNS progression.”
These CNS efficacy results, along with those of the primary analysis showing significantly improved PFS with alectinib in the overall study population, “consolidate alectinib as the new standard of care for patients with previously untreated, advanced ALK+ NSCLC,” the presenter concluded.
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