Phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: primary analysis results.
BACKGROUND
Biliary tract cancer (BTC) has a poor prognosis and lacks a standardized second-line therapy. Vascular endothelial growth factor (VEGF), fibroblast growth factor receptor (FGFR) 4, and platelet-derived growth factor receptor (PDGFR) are highly expressed in BTC. Therefore, lenvatinib (a known inhibitor of VEGF receptors 1-3, FGFRs 1-4, and PDGFR-α) was evaluated for second-line treatment of BTC.


METHODS
In this single-arm, multicenter, open-label, phase 2 study, patients with BTC received lenvatinib 24 mg orally once daily in 28-day cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), PFS rate at 12 weeks, disease control rate, clinical benefit rate, safety and pharmacokinetic profiles.


RESULTS
Twenty-six Japanese patients were enrolled and treated; 3 had a confirmed partial response per investigator assessment and per independent imaging review (IIR); ORR was 11.5% (90% confidence interval [CI]: 3.2-27.2). Median PFS was 3.19 months (95% CI: 2.79-7.23) per investigator assessment and 1.64 months (95% CI: 1.41-3.19) per IIR. Median OS was 7.35 months (95% CI: 4.50-11.27). Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 21 patients (80.8%) and included hypertension (n = 10 [38.5%]), proteinuria (n = 3 [11.5%]), palmar-plantar erythrodysesthesia (n = 3 [11.5%]), decreased appetite (n = 3 [11.5%]), and anemia (n = 3 [11.5%]). Two deaths occurred due to TEAEs between treatment initiation and 30 days after last dose, but neither were considered treatment related.


CONCLUSIONS
Lenvatinib demonstrated antitumor activity in BTC, with a tolerable safety profile, and should be further evaluated as potential second-line therapy for this difficult to treat population.


TRIAL REGISTRATION
ClinicalTrials.gov NCT02579616 . Date of registration: October 19, 2015.
['Ueno|Makoto|M|', 'Ikeda|Masafumi|M|https://orcid.org/0000-0002-4050-2086', 'Sasaki|Takashi|T|', 'Nagashima|Fumio|F|', 'Mizuno|Nobumasa|N|', 'Shimizu|Satoshi|S|', 'Ikezawa|Hiroki|H|', 'Hayata|Nozomi|N|', 'Nakajima|Ryo|R|', 'Morizane|Chigusa|C|']
D000328:Adult D000368:Aged D000970:Antineoplastic Agents D001661:Biliary Tract Neoplasms D005260:Female D005500:Follow-Up Studies D006801:Humans D008297:Male D008875:Middle Aged D010671:Phenylurea Compounds D011379:Prognosis D011804:Quinolines D016879:Salvage Therapy D015996:Survival Rate
Lenvatinib Biliary tract cancer Ampulla of Vater Cholangiocarcinoma Gallbladder cancer