P3.02c-017 ‘2nd Line’ RET-Inhibition in a Female Patient with Non-KIF5B RET-Translocation: Topic: Targeted Therapy

Abstract

RET-rearrangement in unselected non-small cell lung cancer (NSCLC) is expected in 1-2%, most common in adenocarcinomas, young, never or former light smoker. Multikinase Inhibitors such as cabozantinib or vandetanib have shown acitivity against RET-rearranged lung cancer in vitro and in vivo. ORR is about 40% and median duration of response about 8 month with cabozantinib. Progression after RET-inhibition warrants further strategies. 2nd line RET-inhibition might overcome resistance. We report about a 77 year old female patient with primary diagnosis of adenocarcinoma of the lung with malignant pleural effusion, stage IV, in 08/13. EFGR-mutation, ALK- and ROS1-translocation were negative at initial diagnosis. 1st line therapy with carboplatin and paclitaxel resulted in stable disease and clinical deterioration. A VATS was performed with partial resolution of pleural effusion. 2nd line therapy with pemetrexed for 16 months resulted in a clinical benefit (cough and dyspnoe, ECOG raised from 2 to 0). In 07/15 CT scan revealed a dissiminated progression with multiple intrapulmonary nodules, clinically corresponding with cough and dyspnoe again. Molecular diagnostic for cMET, BRAF, KRAS, HER2, PD-L1 revealed no new targets, but a positive RET-FISH testing from initial biopsy. From 10/15 to 03/16 the patient had a good clinical benefit from cabozantinib (multikinase inhibition, including RET). Clinical symptoms resolved in 10 days and ECOG raised from 1 to 0. In 03/16 new hepatic and lymphonodular lesions occurred and the patient suffered again from former clincical symptoms. One cycle gemcitabine was without any benefit. In 04/16 we started with docetaxel 35mg/m2 on day 1 and 8, q3w, combined with nintedanib 200mg twice daily (except day 1 and 8). Again, the patient had an immediate clinical benefit (within 1 week; cough and dyspnoe) and the ECOG raised from 1 to 0. FISH analysis from initial biopsy revealed a non-KIF5B-RET-fusion. This type might show a substatial benefit in the preliminary literature. Nintedanib (plus docetaxel) in a patient with PD on cabozantinib resulted in good clinical response in a patient with a non-KIF5B-RET-mutation. This case illustrates that treatment with a 'second-line' TKI (such as nintedanib) can be effective in RET-rearranged NSCLC.