CHICAGO — The largest database on outcomes with RET-directed therapy for RET-rearranged non-small cell lung cancer (NSCLC) to date confirms RET inhibitors are active in a proportion of patients, a study presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting has shown.1

“Consistent with previous reports, tumor remissions were observed with cabozantinib, vandetanib, and sunitinib,” noted Oliver Gautschi, medical oncologist at Cantonal Hospital Lucerne, Luzern, Switzerland, on behalf of the GLORY investigators.

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A global multicenter network of thoracic oncologists identified patients whose NSCLC was diagnosed as harboring a RET fusion by FISH, RT-PCR, or NGS. Anonymized age, gender, smoking, stage, systemic therapy, and survival data were centrally collected and evaluated by an independent statistician.

“In an analysis of patients treated off-protocol with multikinase inhibitors known to target RET, the primary end point was best objective response (RECIST),” Dr. Gautschi noted.

A total of 132 patients with RET-rearranged NSCLC from the United States, Asia, and Europe were registered in the database. Median age at diagnosis was 61 years (range, 28 to 89 years), 52% were female, 62% were never-smokers, 97% had adenocarcinoma, and 91% had stage III/IV disease.

Of these patients, 41 (31%) had received RET inhibitor therapy off-protocol in the third-line setting (range, 1-8 lines); 14 (34%) had received cabozantinib; 11 (27%), vandetanib; 10 (24%), sunitinib; 2 (5%), sorafenib; 1 (2%), alectinib; 1 (2%), lenvatinib; 1 (2%), nintedanib; and 1 (2%), ponatinib.

Median progression-free survival was 2.9 months (95% confidence interval [CI], 1.3-5.6); median overall survival was 6.8 months (95% CI, 3.9-14.3); and median duration of therapy was 2.2 months (range, 0.5-12.2). A total of 8 patients remained on treatment.

In 35 patients with serial imaging evaluated by RECIST, the overall response rate was 23%; 1 had a complete response; 7, a partial response; 12, stable disease; 14, disease progression; and in 1 patient, disease was not measurable. The disease control rate was 57%.

Individual overall response rates for cabozantinib and vandetanib were 31% and 18%, respectively, and disease control rates were 62% and 46%. No unexpected adverse effects were reported.

“Alongside prospective clinical trials for patients with NSCLC driven by rare genomic alterations, registries can provide complementary information on response to targeted therapies,” they noted.

These results show that new therapeutic approaches and an improved understanding of tumor biology and response are needed.

The registry remains open, both for including patients with RET-targeted therapy as well as follow-up.



1, Gautschi O, Wolf J, Milia J, et al. Targeting RET in patients with RET-rearranged lung cancers: results from a global registry. Poster presentation at: 2016 ASCO Annual Meeting; June 3-7, 2016; Chicago, IL.