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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 Annals of Oncology.
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. doi: 10.1093/annonc/mdy121.
Questions about which next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor is best for treatment-naive ALK+ NSCLC will incite “vigorous debate and the inevitable cross-trial comparison that everyone frowns upon but does anyway,” wrote Misako Nagasaka, MD; Viola W. Zhu, MD, PhD; and Sai-Hong Ignatius Ou, MD, PhD, in an editorial accompanying the study in Annals of Oncology.
Median progression-free survival time in ALUR was 7.1 months, versus 5.4 months in the similarly designed ASCEND-5 trial of second-line ceritinib in ALK+ NSCLC, they noted. “ALUR seems to confirm the superiority of alectinib [over ceritinib] in the post-crizotinib setting.”
Similarly, first-line alectinib produced a longer median progression-free survival time (25.7 months) in the ALEX trial than did first-line ceritinib (16.6 months) in the ASCEND-4 trial, the editorialists noted.
They called brigatinib “the one ALK TKI [anaplastic lymphoma kinase tyrosine kinase inhibitor] that can challenge alectinib.” The global phase 3 Brigatinib 3001 trial will directly compare brigatinib with alectinib in the post-chemotherapy and post-crizotinib setting.
Dr. Nagasaka is with Wayne State University, Detroit; she reported having no conflicts of interest. Dr. Zhu and Dr. Ou are with the University of California, Irvine; they disclosed ties to Roche/Genentech, Pfizer, and Takeda/Ariad. These comments summarize their editorial (Ann Oncol. 2018 Apr 14. doi: 10.1093/annonc/mdy144 )
Questions about which next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor is best for treatment-naive ALK+ NSCLC will incite “vigorous debate and the inevitable cross-trial comparison that everyone frowns upon but does anyway,” wrote Misako Nagasaka, MD; Viola W. Zhu, MD, PhD; and Sai-Hong Ignatius Ou, MD, PhD, in an editorial accompanying the study in Annals of Oncology.
Median progression-free survival time in ALUR was 7.1 months, versus 5.4 months in the similarly designed ASCEND-5 trial of second-line ceritinib in ALK+ NSCLC, they noted. “ALUR seems to confirm the superiority of alectinib [over ceritinib] in the post-crizotinib setting.”
Similarly, first-line alectinib produced a longer median progression-free survival time (25.7 months) in the ALEX trial than did first-line ceritinib (16.6 months) in the ASCEND-4 trial, the editorialists noted.
They called brigatinib “the one ALK TKI [anaplastic lymphoma kinase tyrosine kinase inhibitor] that can challenge alectinib.” The global phase 3 Brigatinib 3001 trial will directly compare brigatinib with alectinib in the post-chemotherapy and post-crizotinib setting.
Dr. Nagasaka is with Wayne State University, Detroit; she reported having no conflicts of interest. Dr. Zhu and Dr. Ou are with the University of California, Irvine; they disclosed ties to Roche/Genentech, Pfizer, and Takeda/Ariad. These comments summarize their editorial (Ann Oncol. 2018 Apr 14. doi: 10.1093/annonc/mdy144 )
Questions about which next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor is best for treatment-naive ALK+ NSCLC will incite “vigorous debate and the inevitable cross-trial comparison that everyone frowns upon but does anyway,” wrote Misako Nagasaka, MD; Viola W. Zhu, MD, PhD; and Sai-Hong Ignatius Ou, MD, PhD, in an editorial accompanying the study in Annals of Oncology.
Median progression-free survival time in ALUR was 7.1 months, versus 5.4 months in the similarly designed ASCEND-5 trial of second-line ceritinib in ALK+ NSCLC, they noted. “ALUR seems to confirm the superiority of alectinib [over ceritinib] in the post-crizotinib setting.”
Similarly, first-line alectinib produced a longer median progression-free survival time (25.7 months) in the ALEX trial than did first-line ceritinib (16.6 months) in the ASCEND-4 trial, the editorialists noted.
They called brigatinib “the one ALK TKI [anaplastic lymphoma kinase tyrosine kinase inhibitor] that can challenge alectinib.” The global phase 3 Brigatinib 3001 trial will directly compare brigatinib with alectinib in the post-chemotherapy and post-crizotinib setting.
Dr. Nagasaka is with Wayne State University, Detroit; she reported having no conflicts of interest. Dr. Zhu and Dr. Ou are with the University of California, Irvine; they disclosed ties to Roche/Genentech, Pfizer, and Takeda/Ariad. These comments summarize their editorial (Ann Oncol. 2018 Apr 14. doi: 10.1093/annonc/mdy144 )
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 Annals of Oncology.
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. doi: 10.1093/annonc/mdy121.
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 Annals of Oncology.
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. doi: 10.1093/annonc/mdy121.
FROM ANNALS OF ONCOLOGY
Key clinical point: Alectinib topped chemotherapy in patients with advanced/metastatic crizotinib-pretreated, ALK-positive NSCLC.
Major finding: 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).
Study details: ALUR, which is a randomized, multicenter, open-label, phase 3 trial of 107 patients.
Disclosures: 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. doi: 10.1093/annonc/mdy121