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Evidence of Intracranial Benefit With Crizotinib in Advanced ALK-Positive NSCLC

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Key Points

  • Crizotinib was associated with a significantly higher intracranial disease control rate among patients with brain metastases in ALK-positive NSCLC.
  • Crizotinib was associated with a nonsignificant improvement in intracranial time to tumor progression

As reported in the Journal of Clinical Oncology, Solomon et al found that crizotinib (Xalkori) was associated with a significantly better disease control rate vs chemotherapy among patients with brain metastases in ALK-positive non–small cell lung cancer (NSCLC). Crizotinib was also associated with a nonsignificant improvement in intracranial time to disease progression. The phase III PROFILE 1014 trial recently showed superior progression-free survival and objective response rate for crizotinib vs pemetrexed (Alimta)/platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC.

Intracranial Activity

Of 343 patients in the intent-to-treat population, 23% had stable treated brain metastases at baseline. Nonsignificant improvements in intracranial time to tumor progression were observed with crizotinib in the intent-to-treat population (hazard ratio [HR] = 0.60, P = .069), patients with treated brain metastases (HR = 0.45, P = .063), and patients without brain metastases (HR = 0.69, P = .323).

Among patients with treated brain metastases, intracranial disease control rates for crizotinib vs chemotherapy were 85% vs 45% at 12 weeks (P < .001) and 56% vs 25% at 24 weeks (P = .006).

Median progression-free survival was significantly longer with crizotinib among patients with treated brain metastases (9.0 vs 4.0 months, HR = 0.40, P < .001), those without brain metastases (11.1 vs 7.2 months, HR = 0.51, P < .001), and in the intent-to-treat population (10.9 vs 7.0 months, HR = 0.45, P < .001).

The investigators concluded: “Compared with chemotherapy, crizotinib demonstrated a significantly higher [intracranial disease control rate] in patients with [treated brain metastases]. Improvements in [intracranial time to tumor progression] were not statistically significant in patients with or without [treated brain metastases], although sensitivity to detect treatment differences in or between the two subgroups was low.”

The study was supported by Pfizer.

Benjamin J. Solomon, MBBS, PhD, of Peter MacCallum Cancer Centre, East Melbourne, Australia, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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