Crizotinib

A study (NCT00585195) screened 1,500 patients with NSCLC for ALK rearrangements and identified 82 patients with advanced ALK-positive disease. Those 82 patients were enrolled in an expanded cohort study instituted after phase I dose escalation had established a recommended dose of crizotinib (250 mg twice a day in 28-day cycles).[32] Most of the patients had received previous treatment.

A study (NCT00585195) screened 1,500 patients with NSCLC for ALK rearrangements and identified 82 patients with advanced ALK-positive disease. Those 82 patients were enrolled in an expanded cohort study instituted after phase I dose escalation had established a recommended dose of crizotinib (250 mg twice a day in 28-day cycles).[32] Most of the patients had received previous treatment.

At a mean treatment duration of 6.4 months, the overall response rate was 57% (47 of 82 patients, with 46 confirmed partial responses, and one confirmed complete response); 27 patients (33%) had stable disease.[32][Level of evidence C2]

A study (NCT00585195) screened 1,500 patients with NSCLC for ALK rearrangements and identified 82 patients with advanced ALK-positive disease. Those 82 patients were enrolled in an expanded cohort study instituted after phase I dose escalation had established a recommended dose of crizotinib (250 mg twice a day in 28-day cycles).[32] Most of the patients had received previous treatment.

The estimated probability of 6-month PFS was 72%.

A study (NCT00585195) screened 1,500 patients with NSCLC for ALK rearrangements and identified 82 patients with advanced ALK-positive disease. Those 82 patients were enrolled in an expanded cohort study instituted after phase I dose escalation had established a recommended dose of crizotinib (250 mg twice a day in 28-day cycles).[32] Most of the patients had received previous treatment.

The 1-year OS rate was 74% (95% CI, 63%–82%), and the 2-year OS rate was 54% (40%–66%).

A study (NCT00585195) screened 1,500 patients with NSCLC for ALK rearrangements and identified 82 patients with advanced ALK-positive disease. Those 82 patients were enrolled in an expanded cohort study instituted after phase I dose escalation had established a recommended dose of crizotinib (250 mg twice a day in 28-day cycles).[32] Most of the patients had received previous treatment.

Survival in 30 patients with ALK variants who were given crizotinib in the second-line or third-line setting was significantly longer than in 23 ALK-positive controls identified from a different cohort given any second-line therapy (median OS, NR [95% CI, 14 months–NR] vs. 6 months [95% CI, 4–17], 1-year OS rate, 70% [95% CI, 50%–83%] vs. 44% [95% CI, 23%–64%], and 2-year OS rate, 55% [33%–72%] vs. 12% [2%–30%]; HR, 0.36; 95% CI, 0.17–0.75; P = .004).[33][Level of evidence C2]

A study (NCT00585195) screened 1,500 patients with NSCLC for ALK rearrangements and identified 82 patients with advanced ALK-positive disease. Those 82 patients were enrolled in an expanded cohort study instituted after phase I dose escalation had established a recommended dose of crizotinib (250 mg twice a day in 28-day cycles).[32] Most of the patients had received previous treatment.

Common toxicities were grade 1 or 2 (mild) gastrointestinal side effects.

A study (NCT00585195) screened 1,500 patients with NSCLC for ALK rearrangements and identified 82 patients with advanced ALK-positive disease. Those 82 patients were enrolled in an expanded cohort study instituted after phase I dose escalation had established a recommended dose of crizotinib (250 mg twice a day in 28-day cycles).[32] Most of the patients had received previous treatment.

Patients with ALK rearrangements tended to be younger than those without the rearrangements; most of the patients had little or no exposure to tobacco; and the patients had adenocarcinomas.

In an open-label, randomized, phase III study, 347 patients with stage IIIB/IV NSCLC and translocations in ALK, who had received one previous regimen of platinum-based chemotherapy, received either crizotinib (250 mg by mouth twice a day) or chemotherapy (pemetrexed 500 mg/m2 if pemetrexed-naïve or docetaxel 75 mg/m2 IV every 21 days). The primary end point was PFS.[34]

In an open-label, randomized, phase III study, 347 patients with stage IIIB/IV NSCLC and translocations in ALK, who had received one previous regimen of platinum-based chemotherapy, received either crizotinib (250 mg by mouth twice a day) or chemotherapy (pemetrexed 500 mg/m2 if pemetrexed-naïve or docetaxel 75 mg/m2 IV every 21 days). The primary end point was PFS.[34]

Median PFS was significantly longer in favor of crizotinib (7.7 months vs. 3.0 months, P < .001).[34][Level of evidence B1]

In an open-label, randomized, phase III study, 347 patients with stage IIIB/IV NSCLC and translocations in ALK, who had received one previous regimen of platinum-based chemotherapy, received either crizotinib (250 mg by mouth twice a day) or chemotherapy (pemetrexed 500 mg/m2 if pemetrexed-naïve or docetaxel 75 mg/m2 IV every 21 days). The primary end point was PFS.[34]

OS, a secondary end point, was not significantly different, but there was significant crossover in the design.