Crizotinib Tops Chemo for ALK-Positive NSCLC With Brain Metastases

Article

First-line crizotinib therapy offered better intracranial disease control rate than chemotherapy in patients with ALK-positive non–small-cell lung cancer (NSCLC) and stable treated brain metastases.

First-line crizotinib therapy offered better intracranial disease control rate (IC-DCR) than chemotherapy in patients with ALK-positive non–small-cell lung cancer (NSCLC) and stable treated brain metastases, according to results of a phase III study.

Earlier results from the ongoing PROFILE 1014 trial showed that crizotinib offers better progression-free survival (PFS) and response rates compared with pemetrexed-platinum chemotherapy. “Although the development of targeted therapies has improved outcomes for selected patient populations with oncogenic driver mutations, brain metastases are frequent and result in significant morbidity and mortality in patients with lung cancer,” wrote study authors led by Benjamin J. Solomon, MBBS, PhD, of the Peter MacCallum Cancer Centre in East Melbourne, Australia.

The new analysis included 343 PROFILE 1014 patients in an intent-to-treat population, 79 of whom (23%) had stable treated brain metastases at baseline; 39 of those patients were treated with crizotinib, and 40 were treated with chemotherapy. The results of the study were published online ahead of print in the Journal of Clinical Oncology.

Among those with brain metastases at baseline, 27% had intracranial progressive disease (IC-PD); the median intracranial time to tumor progression (IC-TTP) was 15.7 months for crizotinib-treated patients and 12.5 months for chemotherapy-treated patients.

Crizotinib was associated with non-significant improvements in IC-TTP in the intent-to-treat population, with a hazard ratio (HR) of 0.60 (95% CI, 0.34–1.05; P = .069); in the brain metastases present group, with an HR of 0.45 (95% CI, 0.19–1.07; P = .063); and in the group without brain metastases, with an HR of 0.69 (95% CI, 0.33–1.45; P = .323).

Crizotinib was significantly associated with better disease control (complete or partial response, or stable disease) than chemotherapy in patients with brain metastases at baseline. The intracranial disease control rate at 12 weeks was 85% with crizotinib and 45% with chemotherapy (P < .001); at 24 weeks, the rates were 56% and 25%, respectively (P = .006). There were four intracranial complete responses with crizotinib, and two with chemotherapy.

In those with brain metastases at baseline, the median PFS with crizotinib was 9 months vs 4 months with chemotherapy, for an HR of 0.40 (95% CI, 0.23–0.69; P < .001). Crizotinib also yielded better PFS in those without brain metastases, with a PFS of 11.1 months vs 7.2 months with chemotherapy, for an HR of 0.51 (95% CI, 0.38–0.69; P < .001). This was also the case in the intent-to-treat population. The median OS had not yet been reached in the intent-to-treat or in the with/without brain metastases groups.

“Prospective assessment of [central nervous system] activity in the PROFILE 1014 study demonstrated superior intracranial disease control by crizotinib over chemotherapy and indicated that crizotinib should be the standard first-line therapy for patients with ALK-positive NSCLC, including those with [brain metastases],” the authors concluded.

Related Videos