1204PD - Phase 2 study of lenvatinib (LN) in patients (Pts) with RET fusion-positive adenocarcinoma of the lung

Date 09 October 2016
Event ESMO 2016 Congress
Session NSCLC, metastatic
Topics Anticancer Agents
Non-Small Cell Lung Cancer
Biological Therapy
Presenter Vamsidhar Velcheti
Citation Annals of Oncology (2016) 27 (6): 416-454. 10.1093/annonc/mdw383
Authors V. Velcheti1, T. Hida2, K.L. Reckamp3, J.C. Yang4, H. Nokihara5, P. Sachdev6, K. Feit6, T. Kubota7, T. Nakada7, C.E. Dutcus6, M. Ren6, T. Tamura8
  • 1Taussig Cancer Institute, Cleveland Clinic, 44195 - Cleveland/US
  • 2Aichi Cancer Center Hospital, Oncology, Nagoya/JP
  • 3City Of Hope, Hospital, Duarte/US
  • 4National Taiwan University Hospital, and National Taiwan University Cancer Center, Taipei City/TW
  • 5National Cancer, Center Hospital, 104-0045 - Tokyo/JP
  • 6Eisai Co., Inc., 07677 - Woodcliff Lake/US
  • 7Eisai Co., Ltd., Tokyo/JP
  • 8Thoracic Center, St. Luke's International Hospital, 104-8560 - Tokyo/JP



Adenocarcinoma, a type of non-small cell lung carcinoma (NSCLC), is one of the most common forms of lung cancer. RET fusions activate RET kinase and occur in 1% to 2% of these pts. LN, a multikinase inhibitor whose targets include RET, may be a treatment option for pts with NSCLC.


This open label, phase 2 study enrolled pts with RET-positive lung adenocarcinoma. Pts received LN 24 mg/d in 28-d cycles until disease progression or unacceptable toxicity. Notably, pts may have received prior RET-targeted therapy. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR; complete response [CR] + partial response [PR] + stable disease [SD, ≥ 7 weeks]), clinical benefit rate (CBR; CR + PR + durable SD [≥23 weeks]), and safety.


25 Pts with RET-positive NSCLC enrolled (KIF5B-RET: 13, other RET fusion: 12). 15 (60%) had ≥2 prior lines of therapy, 7 (28%) had prior RET therapy, and only 2 (8%) had no prior therapy. 16 (64%) were never smokers, 1 (4%) current smoker, 7 (28%) former smokers and 1 (4%) unknown. Tumor shrinkage occurred in the majority of pts; ORR was 16% (confirmed PRs). DCR was 76%. The table shows efficacy data by previous RET therapy. Median duration of treatment was 16 weeks (range: 2–117). Grade ≥3 treatment emergent adverse events (TEAEs) occurred in 23 (92%) pts. Of 3 fatal AEs, 1 was possibly related to LN (pneumonia). TEAEs requiring drug withdrawal, dose reduction, and dose interruption occurred in 5 (20%), 16 (64%), and 19 (76%) pts, respectively. The most common TEAEs included hypertension (68%), nausea (60%), decreased appetite (52%), diarrhea (52%), proteinuria (48%), and vomiting (44%).

Prior RET therapy All Pts n = 25
Yes n = 7 No n = 18
ORR,* n (%) 1 (14) 3 (17) 4 (16)
Median PFS (95% CI), months - - 7.3 (3.6–10.2)
Median OS (95% CI), months - - NE (5.8–NE)
DCR, n (%) 6 (86) 13 (72) 19 (76)
CBR, n (%) 4 (57) 8 (44) 12 (48)

CI, confidence interval; DCR, disease control rate defined as CR + PR + SD lasting ≥ 7 weeks; NE, not evaluable. * All confirmed PRs


LN showed promising clinical activity in pts with RET-positive NSCLC. For most pts, toxicities were manageable with dose modification. These results provide support for LN as a potential treatment for RET-positive NSCLC.

Clinical trial identification


Legal entity responsible for the study

Eisai Inc.


Eisai Inc.


V. Velcheti: Corporate-sponsored research: Merck Inc., Eisai, Genoptix Inc., Genentech, Altor Biosciences, Heat Biologics, Alkermes, Amgen, Nantomics, NanoVision Diagnostics. T. Hida: Corporate sponsored research- Eisai. K.L. Reckamp: Corporate-sponsored research: Eisai Inc., (clinical trial, to institution); editorial assistance. J.C. Yang: Advisory board for: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, AstraZeneca, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, innopharma, Merrimack. H. Nokihara: Clinical trial-Eisai Inc. P. Sachdev, K. Feit, M. Ren: Employee of Eisai Inc. T. Kubota, T. Nakada: Employee of Eisai Co., Ltd., Tokyo Japan. C.E. Dutcus: Employee of Eisai Inc. T. Tamura: Received Honoraria from Eisai.