Crizotinib bests chemo at controlling brain metastases in advanced NSCLC

Crizotinib achieved better control of brain metastases then chemotherapy in a manufacturer-sponsored international open-label phase III randomized trial involving 343 patients with advanced non–small-cell lung cancer (NSCLC), according to a report published March 28 in the Journal of Clinical Oncology.

Even though targeted therapies have greatly improved outcomes for patients whose NSCLC is associated with oncogenic driver mutations, brain metastases remain “a significant clinical problem, resulting in considerable physical and neurocognitive morbidity as well as mortality.” In addition, as patients live longer because of these targeted treatments, the proportion who have brain metastases rises, “such that up to 50% of patients alive at 2 years with EGFR- [epidermal growth factor receptor]–mutated or ALK- [anaplastic lymphoma kinase]–rearranged lung cancer will have brain metastases,” according to Dr. Benjamin J. Solomon of the department of medical oncology, Peter MacCallum Cancer Centre, Melbourne, and his associates.

They compared the efficacy of intracranial disease control between oral crizotinib and IV pemetrexed-platinum chemotherapy in patients who had advanced nonsquamous ALK-positive NSCLC. A total of 79 of these patients (23%) had brain metastases at baseline.

At 12 weeks, a significantly higher percentage of patients achieved intracranial disease control with crizotinib (85%) than with chemotherapy (45%), and the same was true at 24 weeks (56% vs. 25%). Median progression-free survival also was longer with crizotinib, regardless of whether patients had brain metastases at baseline (9 months vs. 4 months) or did not have brain metastases at baseline (11 months vs. 7 months), Dr. Solomon and his associates said (J Clin Oncol. 2016 Mar 28. doi: 10.1200/JCO.2015.63.5888).

Similarly, the overall response rate was significantly higher with crizotinib, regardless of whether patients had brain metastases at baseline (77% vs. 28%) or did not have brain metastases at baseline (74% vs. 50%). In addition, disease progression was less frequent with crizotinib than with chemotherapy in the overall patient population (52% vs. 77%), in the subgroup of patients who had brain metastases at baseline (54% vs. 75%), and in the subgroup of patients who did not have brain metastases at baseline (52% vs. 78%).

These findings indicate that crizotinib should be the standard first-line therapy for patients who have advanced ALK-positive NSCLC, whether or not they have brain metastases, the investigators said.

Crizotinib achieved better control of brain metastases then chemotherapy in a manufacturer-sponsored international open-label phase III randomized trial involving 343 patients with advanced non–small-cell lung cancer (NSCLC), according to a report published March 28 in the Journal of Clinical Oncology.

Even though targeted therapies have greatly improved outcomes for patients whose NSCLC is associated with oncogenic driver mutations, brain metastases remain “a significant clinical problem, resulting in considerable physical and neurocognitive morbidity as well as mortality.” In addition, as patients live longer because of these targeted treatments, the proportion who have brain metastases rises, “such that up to 50% of patients alive at 2 years with EGFR- [epidermal growth factor receptor]–mutated or ALK- [anaplastic lymphoma kinase]–rearranged lung cancer will have brain metastases,” according to Dr. Benjamin J. Solomon of the department of medical oncology, Peter MacCallum Cancer Centre, Melbourne, and his associates.

They compared the efficacy of intracranial disease control between oral crizotinib and IV pemetrexed-platinum chemotherapy in patients who had advanced nonsquamous ALK-positive NSCLC. A total of 79 of these patients (23%) had brain metastases at baseline.

At 12 weeks, a significantly higher percentage of patients achieved intracranial disease control with crizotinib (85%) than with chemotherapy (45%), and the same was true at 24 weeks (56% vs. 25%). Median progression-free survival also was longer with crizotinib, regardless of whether patients had brain metastases at baseline (9 months vs. 4 months) or did not have brain metastases at baseline (11 months vs. 7 months), Dr. Solomon and his associates said (J Clin Oncol. 2016 Mar 28. doi: 10.1200/JCO.2015.63.5888).

Similarly, the overall response rate was significantly higher with crizotinib, regardless of whether patients had brain metastases at baseline (77% vs. 28%) or did not have brain metastases at baseline (74% vs. 50%). In addition, disease progression was less frequent with crizotinib than with chemotherapy in the overall patient population (52% vs. 77%), in the subgroup of patients who had brain metastases at baseline (54% vs. 75%), and in the subgroup of patients who did not have brain metastases at baseline (52% vs. 78%).

These findings indicate that crizotinib should be the standard first-line therapy for patients who have advanced ALK-positive NSCLC, whether or not they have brain metastases, the investigators said.

Crizotinib achieved better control of brain metastases then chemotherapy in a manufacturer-sponsored international open-label phase III randomized trial involving 343 patients with advanced non–small-cell lung cancer (NSCLC), according to a report published March 28 in the Journal of Clinical Oncology.

Even though targeted therapies have greatly improved outcomes for patients whose NSCLC is associated with oncogenic driver mutations, brain metastases remain “a significant clinical problem, resulting in considerable physical and neurocognitive morbidity as well as mortality.” In addition, as patients live longer because of these targeted treatments, the proportion who have brain metastases rises, “such that up to 50% of patients alive at 2 years with EGFR- [epidermal growth factor receptor]–mutated or ALK- [anaplastic lymphoma kinase]–rearranged lung cancer will have brain metastases,” according to Dr. Benjamin J. Solomon of the department of medical oncology, Peter MacCallum Cancer Centre, Melbourne, and his associates.

They compared the efficacy of intracranial disease control between oral crizotinib and IV pemetrexed-platinum chemotherapy in patients who had advanced nonsquamous ALK-positive NSCLC. A total of 79 of these patients (23%) had brain metastases at baseline.

At 12 weeks, a significantly higher percentage of patients achieved intracranial disease control with crizotinib (85%) than with chemotherapy (45%), and the same was true at 24 weeks (56% vs. 25%). Median progression-free survival also was longer with crizotinib, regardless of whether patients had brain metastases at baseline (9 months vs. 4 months) or did not have brain metastases at baseline (11 months vs. 7 months), Dr. Solomon and his associates said (J Clin Oncol. 2016 Mar 28. doi: 10.1200/JCO.2015.63.5888).

Similarly, the overall response rate was significantly higher with crizotinib, regardless of whether patients had brain metastases at baseline (77% vs. 28%) or did not have brain metastases at baseline (74% vs. 50%). In addition, disease progression was less frequent with crizotinib than with chemotherapy in the overall patient population (52% vs. 77%), in the subgroup of patients who had brain metastases at baseline (54% vs. 75%), and in the subgroup of patients who did not have brain metastases at baseline (52% vs. 78%).

These findings indicate that crizotinib should be the standard first-line therapy for patients who have advanced ALK-positive NSCLC, whether or not they have brain metastases, the investigators said.