de la Torre-Aláez M, Matilla A, Varela M, Iñarrairaegui M, Reig M, Lledó JL, Arenas JI, Lorente S, Testillano M, Márquez L, Da Fonseca L, Argemí J, Gómez-Martin C, Rodriguez-Fraile M, Bilbao JI, and Sangro B
Purpose: To evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in combination with a PD-1 inhibitor in patients with unresectable hepatocellular carcinoma (uHCC) and liver-only disease ineligible for chemoembolization., Patients and Methods: NASIR-HCC is a single-arm, multicenter, open-label, phase 2 trial that recruited from 2017 to 2019 patients who were naïve to immunotherapy and had tumors in the BCLC B2 substage (single or multiple tumors beyond the up-to-7 rule), or unilobar tumors with segmental or lobar portal vein invasion (PVI); no extrahepatic spread; and preserved liver function. Patients received SIRT followed 3 weeks later by nivolumab (240 mg every 2 weeks) for up to 24 doses or until disease progression or unacceptable toxicity. Safety was the primary endpoint. Secondary objectives included objective response rate (ORR), time to progression (TTP), and overall survival (OS)., Results: 42 patients received SIRT (31 BCLC-B2, 11 with PVI) and were followed for a median of 22.2 months. 27 patients discontinued and 1 never received Nivolumab. 41 patients had any-grade adverse events (AE) and 21 had serious AEs (SAE). Treatment-related AEs and SAEs grade 3-4 occurred in 8 and 5 patients, respectively. Using RECIST 1.1 criteria, ORR reported by investigators was 41.5% (95% CI 26.3% to 57.9%). Four patients were downstaged to partial hepatectomy. Median TTP was 8.8 months (95% CI 7.0 to 10.5) and median OS was 20.9 months (95% CI 17.7 to 24.1)., Conclusions: The combination of SIRT and nivolumab has shown an acceptable safety profile and signs of antitumor activity in the treatment of patients with uHCC that were fit for SIRT., Trial Registration Number: NCT03380130., Competing Interests: Competing interests: MdlTA: travel grants from ESAI, Bayern and Pfizer. AM: consultancy fees from Astra-Zeneca, Bayer, Eisai-MSD, Roche and Sirtex Medical; and travel expenses from Astra-Zeneca, Bayer and Boston Scientific. MV: consultancy fees from Astra-Zeneca, Bayer, Eisai-MSD, BMS and Roche; honoraria from Bayer, Boston, Gilead, Eisai-MSD and Abbvie; and travel expenses from Astra-Zeneca and Bayer. MI: lecture fees and travel support from BMS. MR: consultancy fees from Astra Zeneca, Bayer, BMS, Boston Science, Ipsen, Lilly and Roche; lecture fees from Bayer, BMS, Gilead, Lilly, Roche and UniversalDX; travel support from Astra-Zeneca, Bayer, BMS and Lilly; research funding (to institution) from Bayer and Ipsen. JLL: speaker fees from Bayer and EISAI-MSD; consultancy fees from Bayer, EISAI-MSD and Roche. JIA: none. Sara Lorente: none. Milagros Testillano: travel expenses from Abbvie. LM: speaker fees from Bayer, Eisai and Gilead; advisory fees from Eisai and MSD. LDF: speaker fees from Bayer, BMS, Ipsen and Roche. JA: none. CG-M: consultancy or advisory fees from Amgen, Astra-Zeneca, BMS, EISAI, Hengrui Therapeutics, MERCK, and Roche-Spain; speaker fees from EISAI and Eli-Lilly. MR-F: consultancy and speaker fees from Sirtex Medical. JIB: consultancy fees from Boston Scientific, MSD, Sirtex Medical and Terumo; speaker fees from Sirtex; research grants from Sirtex and Terumo. BS: consultancy fees from Adaptimmune, Astra Zeneca, Bayer, BMS, Boston Scientific, BTG, Eisai, Eli Lilly, H3 Biomedicine, Ipsen, Novartis, Merck, Roche, Sirtex Medical and Terumo; speaker fees from Astra Zeneca, Bayer, BMS, BTG, Eli Lilly, Ipsen, Novartis, Merck, Roche, Sirtex Medical and Terumo; research grants (to Institution) from BMS and Sirtex Medical., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)