Study findings being presented at the virtual 2020 ASCO Annual Meeting posit local consolidative therapy (LCT) with brigatinib as a safe and effective treatment option for patients with ALK-rearranged advanced NSCLC, regardless of the number of metastatic sites.

“Approximately, 95% of patients who have an initial response to ALK-TKIs exhibit an incomplete response resulting in residual disease that enables the emergence of acquired resistance. Eliminating residual disease using LCT may delay resistance emergence and improve clinical outcomes,” wrote Yasir Elamin, MD, The University of Texas MD Anderson Cancer Center, Houston, and colleagues.

Thus, Dr Elamin et al sought to evaluate the safety, feasibility, and efficacy of treating patients in this setting with brigatinib for an induction period of 8 weeks followed by LCT with radiation and/or surgery.

Between December 2018 and January 2020, a total of 17 TKI-naïve patients (median age, 55 years) with ALK-rearranged advanced NSCLC and any number of metastases were enrolled in the single-center study. At baseline, 15 of these patents had polymetastatic and the remaining 2 had oligometastatic disease.

Among 16 patients evaluated for response who completed LCT (including radiotherapy, n = 11; surgery, n = 3; and surgery plus radiotherapy; n = 2) as of February 1, 2020, the rate of disease control was 100%, with an objective response rate of 94% (n = 15).

The median follow-up time frame was 8 months, and no patients have had disease progression to date. Four of the 5 patients who underwent surgery had a lobectomy and mediastinal lymph node dissection (MLND), 1 had wedge resection with MLND, and 1 had adrenalectomy; 2 of these patients had complete pathological responses with 1 occurring at the primary tumor.

There were no adverse events (AEs) grade ≥2 related to LCT. Severe AEs related to brigatinib therapy included grade 3 nausea and increased blood levels of creatine kinase, lipase, alanine aminotransferase, amylase (n = 1 each).

One patient was reported as having grade 2 pneumonitis 2 weeks after initiating brigatinib, but this AE was resolved with steroids and brigatinib was resumed at a lower dose.

“Brigatinib with LCT is safe and feasible in patients with ALK-rearranged advanced NSCLC irrespective of number of metastatic sites,” Dr Elamin and co-investigators wrote.

“Brigatinib and LCT may be an effective therapeutic strategy in this subset of NSCLC patients,” they concluded.—Hina M. Porcelli

Elamin Y, Gandhi S, Antonoff M, et al. BRIGHTSTAR: A pilot trial of local consolidative therapy (LCT) with brigatinib in tyrosine kinase inhibitor (TKI)-naïve ALK-rearranged advanced NSCLC. Presented at: the 2020 ASCO Annual Meeting; May 29-31, 2020. Abstract 9624.