Abstract 1917P
Background
Lenvatinib is approved for patients with RAIR DTC. While the overall response rate (ORR) is high, few patients achieve a complete response (CR) and most patients eventually have progressive disease (PD). Combination lenvatinib and pembrolizumab is being explored in many different cancers. The purpose of this study was to assess the potential value of adding pembrolizumab to RAIR DTC patients who were progressing on single-agent lenvatinib therapy.
Methods
Patients with RAIR DTC with Response Evaluation Criteria in Solid Tumor (RECIST v1.1) measurable PD on lenvatinib therapy were enrolled in this single-arm study. Patients were excluded if they had received more than one prior VEGFR-directed multikinase therapy. Pembrolizumab was given 200mg IV every 3 weeks. The primary endpoint was ORR. Clinical benefit rate (CBR=ORR+SD), progression-free survival (PFS) and safety graded by CTCAE v4.0 were secondary endpoints.
Results
Twenty-seven patients were enrolled and 25 were eligible and received treatment. The median age was 60.0 years. 88.0% of patients had received other VEGFR therapy prior to lenvatinib. The median dose of lenvatinib at entry was 14 mg daily (10-24 mg). Thirty-six percent of patients had grade 3 adverse events (AEs) and no patients had grade 4 AEs. There were no treatment-related deaths. The most common grade 3 AEs were dyspnea (12%), and hypertension (12%). All other grade 3 AE were ≤ 4%. One patient had grade 3 myocarditis and heart failure that was likely related to pembrolizumab therapy. Of 20 evaluable patients, 3 (15%) had a partial response (PR) and 17 (85%) had stable disease (SD), for an ORR of 15% and CBR of 100%. Median PFS was 12.6 months (95% CI: 7.1-18.2). The PFS at 12 months was 56%. Eleven patients (44%) are still on treatment (1.6-16.8 mo). Three patients (15%) had >40% target tumor shrinkage.
Conclusions
Adding pembrolizumab to lenvatinib therapy is well tolerated in patients with RAIR DTC. A preliminary primary endpoint of ORR was 15%. The addition of pembrolizumab to patients progressing on lenvatinib has a high CBR and favorable PFS in patients with RAIR DTC.
Clinical trial identification
NCT02973997.
Editorial acknowledgement
Legal entity responsible for the study
International Thyroid Oncology Group (ITOG) Academic and Community Cancer Research United (ACCRU).
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc Eisai, Inc International Thyroid Oncology Group (ITOG).
Disclosure
B. Konda: Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Xencor; Research grant/Funding (institution): BMS. E.J. Sherman: Advisory/Consultancy, Research grant/Funding (institution): Regeneron; Advisory/Consultancy, Research grant/Funding (institution): Loxo; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Eisai; Research grant/Funding (institution): Plexxicon. R. Dadu: Honoraria (self), Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: BMS. A.G. Gianoukakis: Advisory/Consultancy: Eisai; Advisory/Consultancy: Lilly; Advisory/Consultancy: Loxo; Advisory/Consultancy: Bayer. L.J. Wirth: Honoraria (self), Research grant/Funding (institution): LOXO Oncology; Honoraria (self): Bayer; Honoraria (self): Blueprint Medicine; Honoraria (self): Cue Biopharma; Honoraria (self): Eisai; Honoraria (self): Exelixis; Honoraria (self): Genentech; Honoraria (self): Lilly; Honoraria (self): Merck; Honoraria (self): Rakuten Medical. All other authors have declared no conflicts of interest.