Crizotinib improved survival in advanced, ALK-positive NSCLC

Issue: July 25, 2011

2011 ASCO Annual Meeting

CHICAGO — Results from an analysis of patients with advanced, ALK-positive non-small cell lung cancer showed that those treated with crizotinib had superior OS when compared with historical controls.

Though the results are promising, Alice T. Shaw, MD, PhD, attending physician in the thoracic cancer program at Massachusetts General Hospital, stressed that these findings require further validation. She presented the results during the 2011 ASCO Annual Meeting.

“This type of analysis is a little bit limited because it wasn’t from a randomized, controlled study, but the results suggest that crizotinib may significantly improve survival,” Shaw told HemOnc Today.

In an earlier phase-1 trial by Kwak et al, crizotinib, an ALK tyrosine kinase inhibitor, showed strong antitumor activity in patients with advanced, ALK-positive NSCLC. However, that study did not produce OS data.

To determine whether crizotinib effected survival, Shaw et al examined OS in 82 patients enrolled in an expansion cohort of that original phase-1 trial. They then compared OS data with 37 ALK-positive patients from phase 1 sites who were not treated with crizotinib, as well as 253 ALK-negative/EGFR-negative patients from a single site.

Both groups were similar in median age, sex, smoking history, presence of brain metastases at any time, number of prior therapies and types of prior chemotherapy.

One-year OS for patients assigned to crizotinib was 74% and 2-year OS was 64%. Median OS has not been reached. Among the 37 ALK-positive controls, 1-year OS was 73% and 2-year OS was 33%. Median OS was 20 months.

Among 32 patients treated with second- and third-line crizotinib, researchers found that 1-year OS was 71% vs. 46% for 24 ALK-positive patients not treated with crizotinib. Two-year OS similarly favored the crizotinib group, 61% vs. 9%. One-year OS was 49% and 2-year OS was 33% for 123 ALK-negative patients in the second-line setting. Median OS was 11 months in both non-crizotinib groups.

Shaw said researchers are already recruiting 318 patients into a randomized, controlled trial to confirm these findings. She hopes to have final results in 2013. – by Jason Harris

For more information:

Shaw AT. # TPS212. Presented at: 2011 ASCO Annual Meeting; June 3-7; Chicago.

Disclosure: Dr. Shaw reported serving in a consultant or advisory role for Pfizer, and receiving research funding from AstraZeneca, Novartis and Pfizer.

What we’re able to do is take an abnormality in a tumor and find a therapy that really helps the patients who have tumors with the ALK mutation. We have a target, we have a treatment for that target, and patients who get to that treatment – even though so far it’s only been through a clinical trial – will have a better outcome. Now we have to wait for the regulatory authorities to decide there is enough data showing crizotinib is safe and effective, and I think we’ll see that in the next six months.

- Greg A. Masters, MD
Medical Oncologist at the Christiana Care Helen F. Graham Cancer Center, Newark, Del.

Disclosure: Dr. Masters reported no relevant financial disclosures.

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