Crizotinib superior to chemotherapy in advanced, ALK-positive NSCLC

Issue: February 25, 2015

Patients with advanced, ALK-positive non–small cell lung cancer who received first-line treatment with crizotinib demonstrated improved outcomes compared with those treated with pemetrexed and platinum chemotherapy, according to results of a phase 3 study.

Benjamin J. Solomon, MB, BS, PhD, of Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues evaluated data from 343 treatment-naive patients with advanced ALK-positive nonsquamous NSCLC.

Researchers randomly assigned patients to receive 250 mg twice daily crizotinib (Xalkori, Pfizer; n=172) or chemotherapy (n=171) every 3 weeks for six cycles. Patients assigned chemotherapy received 500 mg/m²pemetrexed (Alimta, Lilly) plus 75 mg/m² cisplatin or carboplatin (area under the curve, 5 mg to 6 mg/milliliter/minute).

Median follow-up was 17.4 months for patients assigned crizotinib and 16.7 months for patients assigned chemotherapy.

Researchers reported a significantly higher response rate (74% vs. 45%; P˂.001) and a longer median duration of response (11.3 months vs. 5.3 months) in the crizotinib arm.

Patients assigned crizotinib also demonstrated significantly longer median PFS (10.9 months vs. 7 months), as well as a significantly reduced risk for progression or death (HR=0.45; 95% CI, 0.35-0.6).

Median OS had not been reached in either arm at the time of the analysis, although the probability of 1-year survival was slightly higher in the crizotinib arm (84% vs. 79%).

Crizotinib did not significantly reduce the risk for death compared with chemotherapy (HR=0.82; 95% CI, 0.54-1.26); however, researchers noted these data are affected by the fact that 70% of patients in the chemotherapy arm crossed over to treatment with crizotinib. Analyses adjusted for crossover demonstrated an HR of 0.6 (95% CI, 0.27-1.42) for death with crizotinib using the Wilcoxon test and an HR of 0.67 (95% CI, 0.28-1.48) for death with crizotinib using the log-rank test.

More patients assigned crizotinib experienced vision disorder (71% vs. 9%), diarrhea (61% vs. 13%) and edema (49% vs. 12%), whereas more patients assigned chemotherapy experienced fatigue (38% vs. 29%), anemia (32% vs. 9%) and neutropenia (30% vs. 21%).

Fourteen percent of patients in the crizotinib arm and 2% of patients in the chemotherapy arm experienced grade 3 or 4 elevations of aminotransferase levels, but researchers noted the elevations were managed by dose interruptions or reductions.

Patients who received crizotinib achieved significantly greater improvements from baseline in global quality of life scores (P˂.001) and in physical, social, emotional and role functioning domains (P˂.001). Crizotinib also was associated with a significant delay in the worsening of lung-cancer symptoms (HR=0.62; 95% CI, 0.47-0.8).

“In patients with previously untreated ALK-positive NSCLC, crizotinib treatment was superior to pemetrexed-plus-platinum chemotherapy with respect to PFS, objective response rate, reduction of lung-cancer symptoms and improvement in quality of life,” Solomon and researchers concluded.

Disclosure: The study was funded by Pfizer. See the study for a list of the researchers’ relevant financial disclosures.

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Source: Solomon BJ. N Engl J Med. 2014;371:2167-2177.