Crizotinib versus chemotherapy in advanced ALK-positive lung cancer.

By A. Shaw, Dong-Wan Kim, K. Nakagawa, T. Seto, L. Crinò, M. Ahn, T. D. De Pas, B. Besse, B. Solomon, F. Blackhall and 13 more. New England Journal of Medicine, 2013

3,336 citations recorded by the source corpus.

BACKGROUND In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. METHODS We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival. RESULTS The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy. CONCLUSIONS Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.).

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/fa066da9a628c8757e231c0ace3b361f8d722321

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Citations in the corpus

Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. (2015, background): “Overall patients still reported superior reduction of symptoms and improvements in overall quality of life with crizotinib (101).”
Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastases. (2015, positive): “More recently, the randomized phase III PROFILE 1007 trial showed that for previously treated patients with ALK-rearranged NSCLC, crizotinib led to improved outcomes (progression-free survival [PFS; primary outcome], objective response rate [ORR], and quality-of-life measurements) when compared with”
Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations (2015, neutral): “(%) [95% CI] 8 (42) [20–67] 0 1 (4) [<1–20] 1 (12) [<1–53] 6 (43) [18–71] 2 (29) [4–71]”
Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study. (2016, neutral): “Any cause, in $ 10% Patients Constipation 39 (28) 6 (4) 0 0 45 (33) Fatigue 26 (19) 8 (6) 2 (1) 0 36 (26) Peripheral edema 27 (20) 6 (4) 1 (1) 0 34 (25) Myalgia 25 (18) 5 (4) 1 (1) 0 31 (23) Asthenia 16 (12) 8 (6) 1 (1) 0 25 (18) Headache 16 (12) 4 (3) 2 (1) 0 22 (16) Cough 15 (11) 4 (3) 0 0 19 (14)”
Immune Checkpoint Targeting in Cancer Therapy: Towards Combination Strategies with Curative Potential (2015, background): “, 2010), was shown to elicit a response rate of 65%with a median duration of response of less than 8 months in a phase III trial (Shaw et al., 2013).”
Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2018, background): “The benefit of improvement in ORR and PFS is consistent across all age groups, genders, smoking status and PS. Notably, none of the above studies have shown any benefit in OS for an EGFR TKI over platinum-based ChT, likely due to the high level of crossover.”
Ceritinib in ALK-Rearranged Non–Small-Cell Lung Cancer (2014, neutral): “Elevated aspartate aminotransferase level 0 1 (7) 0 0 3 (60) 10 (12) 14 (11)”