Crizotinib superior to single-agent chemotherapy for ALK-positive advanced NSCLC

Crizotinib proved more effective than standard chemotherapy for patients with advanced, ALK-positive non–small-cell lung cancer, according to phase 3 study results presented at the 2012 Congress of the European Society for Medical Oncology in Vienna.

“This study is the first head-to-head comparison of crizotinib with standard chemotherapy in this patient group,” lead researcher Alice T. Shaw, MD, PhD, thoracic oncologist at Massachusetts General Hospital Cancer Center in Boston, said in a press release.

Previous uncontrolled studies showed crizotinib (Xalkori, Pfizer) produced significant clinical responses in patients with advanced ALK-positive NSCLC.

To determine the efficacy and safety of crizotinib compared with standard chemotherapy as a second-line therapy, Shaw and colleagues initiated a study of 347 patients with stage IIB/IV ALK-positive lung cancer who underwent prior treatment with platinum-based chemotherapy.

The researchers randomly assigned patients to crizotinib 250 mg orally twice daily (n=173) or chemotherapy three times a week (n=174). Of those who received chemotherapy, 58% received pemetrexed 500 mg/m² and 42% received docetaxel 75 mg/ m² intravenously.

Patients who exhibited progressive disease after undergoing chemotherapy were later offered crizotinib.

PFS by independent radiologic review served as the primary endpoint. Secondary endpoints included objective response rate, OS, safety and patient-reported outcomes.

Median PFS among patients assigned to crizotinib was 7.7 months compared with 3 months for patients assigned to chemotherapy (HR=0.49; 95% CI, 0.37-0.64; P<0.0001). The overall response rate also was significantly higher in those treated with crizotinib compared with chemotherapy (65% vs. 20%; P<0.0001).

The drug also exhibited an acceptable safety profile, the researchers said.

“In ALK-positive patients who have been previously treated with first-line, platinum-based chemotherapy, crizotinib is superior to standard single-agent chemotherapy in terms of response, progression-free survival and quality of life,” Shaw said. “These results establish crizotinib as the standard of care for patients with advanced, previously treated, ALK-positive lung cancer.”

There was significant crossover in the study. The majority of patients in the chemotherapy arm ultimately received crizotinib after disease progression, Shaw said.

“This makes determination of overall survival benefit very challenging,” Shaw said.

The most common adverse events reported by patients who received crizotinib included diarrhea, nausea, vomiting and elevated transaminases, while patients who received standard chemotherapy reported nausea, fatigue, neutropenia, decreased appetite and alopecia.

“Patients still reported improved quality of life on crizotinib compared with chemotherapy,” Shaw said.

Researchers reported a 31% rate of grade-3/grade-4 treatment-related adverse events in each arm. However, only 6% of patients assigned to crizotinib discontinued the trial due to treatment-related adverse events compared with 10% of patients assigned to chemotherapy.

For more information:

Shaw AT. Abstract #1 LBA. Presented at: 2012 European Society for Medical Oncology Congress; Sept.  28 – Oct. 2, 2012; Vienna, Austria.

Disclosure: The researchers report no relevant financial disclosures.


Enriqueta Felip

  • The results of this study are of great clinical relevance. Crizotinib, an oral drug, is more effective than standard chemotherapy in previously treated lung cancer patients with a specific molecular alteration, ALK. This is the first randomized study in a group of lung cancer patients selected precisely because they have ALK-positive tumors. After the worldwide implementation of targeted therapy in lung cancer patients defined by another molecular alteration, EGFR mutation, this is the second group of lung cancer patients to clearly benefit from a therapy directly targeting a molecular alteration. The results of this study represent a significant step toward individualized therapy in lung cancer patients.

    • Enriqueta Felip, MD, PhD
    • Head of the lung cancer unit
      Department of Oncology
      Vall d'Hebron University Hospital
      Barcelona, Spain
  • Disclosures: Felip reports no relevant financial disclosures.

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