Local Ablation Extends Therapy Duration for Patients with NSCLC, Improves Disease Control

February 2013, Vol 4, No 2

Boston, MA—Patients with ALK-positive non–small-cell lung cancer (NSCLC) continued with crizotinib therapy more than twice as long when drug-resistant lesions were managed with local ablation, as shown by the results of a small clinical trial presented at the 2012 American Society for Radiation Oncology meeting.

"The traditional therapeutic paradigm has been to change therapies at progression, regardless of how limited the progression might be,” said Gregory Gan, MD, PhD, a radiation oncology resident at the University of Colorado in Aurora. “We asked whether a better alternative might exist to help patients remain on otherwise effective systemic targeted therapy.”

The time for receiving treatment averaged approximately 10 months in patients who did not receive ablative therapy compared with 21 months in patients who underwent ablative therapy for discrete lesions.

All of the patients who received ablative therapy had disease control at 6 months, and 10 of 12 patients had no progression after 12 months.

Local ablation has potential application in a substantial fraction of patients with NSCLC who have good overall disease control, except for isolated pockets of resistance, a phenomenon known as “oligoprogression,” according to this retrospective review of medical records for 38 patients with ALK-positive NSCLC who received crizotinib (Xalkori).

Subsequently, 12 patients had local ablation (radiation or surgery) of a total of 26 lesions. The remaining 26 patients were treated according to the conventional paradigm.

The 12 patients who had ablative therapy used crizotinib continuously, taking a break only on the day of the ablation.

Progression-free survival (PFS) in crizotinib-treated patients ranged from 8 to 10 months. The 12 patients who had ablative treatment had a mean PFS of 10 months. After ablation of isolated lesions, the patients continued to receive crizotinib for an additional 11 months.

Dr Gan and colleagues examined the relationship between biological equivalent dose (BED) of radiation and disease control. The median BED was 58.6 Gy. The best disease control occurred in patients treated to a BED of >100 Gy. Other measures of effective dose delivered also suggested better control with higher doses.

The investigators published expanded results in December (Weickhardt AJ, et al. J Thorac Oncol. 2012;7:1807-1814). The study population had expanded to 65 patients, including some treated with the epidermal growth factor receptor (EGFR) inhibitor erlotinib.

The median time to progression was 9.0 months with crizotinib and 13.8 months among patients with EGFR mutations who were treated with erlotinib (Tarceva).

Of the 51 patients who progressed on therapy, 25 met the criteria for local ablative therapy. All but 1 of the patients had irradiation as ablative therapy.

After local ablative therapy, 19 of the 25 patients progressed again after a median follow-up of 6.2 months.

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