3-Year Follow-up of Japanese Trial of Alectinib in ALK-Positive NSCLC


Key Points

  • In previously treated patients with ALK-positive NSCLC, 3-year rates were 62% for progression-free survival and 78% for overall survival.
  • No correlation was observed for tumor shrinkage and progression-free survival.

Promising 3-year outcomes were found in patients from a Japanese phase I/II study of alectinib (Alecensa) in previously treated patients with ALK-positive non–small cell lung cancer (NSCLC). The findings were reported by Tamura et al in the Journal of Clinical Oncology.

Study Details

In the study, 46 patients with ALK inhibitor–naive disease who had progressed after at least 1 regimen of previous chemotherapy received alectinib at 300 mg twice per day in the phase II portion of the study. In total, 52% of patients had received at least 2 prior regimens. At the updated cutoff in September 2015 (first patient enrolled in August 2011), 25 patients were still receiving alectinib.

Progression-Free and Overall Survival

Disease progression occurred in 18 patients (39%). Median progression-free survival had not been reached; the 3-year rate was 62% (95% confidence interval [CI] = 45%–75%). Of 14 patients with brain metastases at baseline, 6 (43%) remained in the study without central nervous system or systemic disease progression.

Assessment of subgroups according to brain metastases, disease stage, number of previous chemotherapy regimens, smoking history, and sex showed that median progression-free survival was reached only among the 14 patients with brain metastases (38 months, 95% CI = 9 months to not reached) and among the 22 male patients (35.3 months, 95% CI = 18 months to not reached). Scatter plotting of tumor shrinkage and progression-free survival showed no apparent correlation between the two.

The 3-year overall survival rate was 78%, with median overall survival not being estimable.

Of 21 patients who withdrew from the trial before data cutoff, 17 received further systemic therapies, including 12 who received an ALK inhibitor other than alectinib.

Adverse Events

The most common treatment-related adverse event of any grade among all 56 patients in the phase I and II portions of the trial were increased blood bilirubin (36.2%). dysgeusia (34.5%), increased aspartate transaminase (32.8%), increased blood creatinine (32.8%), and constipation (31.0%). Grade 3 adverse events (no grade 4 or 5 events observed) were reported in 50% of phase II patients, and serious adverse events were noted in 21.7%. Treatment-related grade 3 adverse events occurred in 27.1% of the entire safety population, with the most common being decreased neutrophil count (6.9%) and increased bilirubin, increased alanine transaminase, and increased creatine phosphokinase (3.4% each). The majority of adverse events had an onset within the first 6 months of treatment, although the onset of diarrhea continued throughout treatment.

A total of 15 of the 46 phase II patients were being treated for cancer pain, cough, or sputum production at baseline. Most symptoms were relieved early in alectinib treatment, and the drugs used to treat these symptoms were able to be dramatically decreased over the course of the study.

The investigators concluded: “Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment.”

The study was supported by Chugai Pharmaceutical.

Tomohide Tamura, MD, of St. Luke’s International Hospital, Tokyo, is the corresponding author of the Journal of Clinical Oncology article.

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