TY - JOUR
T1 - Five-year overall survival with ipilimumab and stereotactic ablative radiotherapy for metastatic disease
AU - He, Kewen
AU - Hong, David S.
AU - Tang, Chad
AU - Sezen, Duygu
AU - Cox, Livia
AU - Maleki, Aurian
AU - Bertolet, Genevieve
AU - Nguyen, Quynh Nhu
AU - Comeaux, Nathan I.
AU - Schuda, Lily
AU - Chen, Dawei
AU - Welsh, James W.
N1 - Funding Information:
Dr. Hong declares grants from AbbVie, Aldi- Norte, Astra-Zeneca, BMS, Daiichi-Sankyo, Eisai, Fate Therapuetics, Genmab, GSK, Ignyta, Kite, Kyowa, Eli Lilly, LOXO, Merk, MedImmune Mirati, miRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Seattle Genetics, Turning Point Therapeutics; personal fees from Alpha Insights, Axiom, Baxter, eCancer, GLG, Group H, Guidepoint, Liberium, Medscape, Numab, Oncology Education Pro- ject Association, Prime Oncology, Trieza Therapuetics, WebMD; grants and personal fees from Adaptimmune, Amgen, Bayer, Genentech, Infinity, Pfizer, Takeda. Non-financial support from AACR, ASCO, POET, CCLO, SITC; advisor for Molecular Match, OncoResponse, Presagia Inc. Dr. Tang is an Andrew Sabin Fellow. He has received personal fees from Bayer and royalties from Wolter Kluwer publishing company. Additional grant support from DOD and CPRIT. Dr. Welsh reports research support from GlaxoSmithKline, Bristol Meyers Squibb, Merck, Nanobiotix, RefleXion, Alkermes, Artidis, Mavu Pharma, Takeda, and Checkmate Pharmaceuticals. Dr. Welsh serves on the scientific advisory board for Legion Healthcare Partners, RefleXion Medical, MolecularMatch, Merck, AstraZeneca, Aileron Therapeutics, OncoResponse, Checkmate Pharmaceuticals, Mavu Pharma, Alpine Immune Sciences, Ventana Medical Systems, Nanobiotix, China Medical Tribune, GI Innovation, Genentech and Nanorobotics. JWW is on Speaking Engagements for Ventana Medical Systems, US Oncology, Alkermes, and Boehringer Ingelheim. He is co-founder of Healios, MolecularMatch, OncoResponse and serves as an advisor to Astra Zeneca, OncoResponse, Merck, MolecularMatch, Incyte, Aileron and Nanobiotix. Dr. Welsh Dr. Welsh holds stock or ownership in Alpine Immune Sciences, Checkmate Pharmaceuticals, Healios, Mavu Pharma, Legion Healthcare Partners, MolecularMatch, Nanorobotics, OncoResponse, and RefleXion. Dr. Welsh has accepted honoraria in the form of travel costs from Nanobiotix, RefleXion, Varian, Shandong University, The Korea Society of Radiology, Aileron Therapeutics and Ventana. Dr. Welsh has the following patents; MP470 (amuvatinib), MRX34 regulation of PDL1, XRT technique to overcome immune resistance. MD Anderson Cancer Center has a trademark for RadScopal TM . The rest of the authors disclosed no competing interests.
Funding Information:
This work was funded by Bristol-Myers Squibb.
Publisher Copyright:
© 2023 The Authors
PY - 2023/6
Y1 - 2023/6
N2 - Purpose: Ipilimumab plus stereotactic ablative radiotherapy (SABR) demonstrate satisfactory short-term clinical benefit and low toxicities in metastatic cancers. Here, we report the 5-year overall survival (OS) rates for patients with metastatic disease treated with this combined-modality therapy in a phase II trial (NCT02239900). Methods and materials: SABR was delivered to patients with metastatic lesions in the liver and lung either during the first dose (concurrent) or 1 week after the second dose (sequential) of ipilimumab (every 3 weeks for 4 cycles). SABR was administered to liver or lung metastases as 50 Gy in 4 fractions or 60 Gy in 10 fractions, considering the tumor location. The OS rates at 12, 36, and 60 months were estimated by the Kaplan-Meier method; subgroup analyses of progression-free survival (PFS) and OS by SABR-targeted lesions (liver/lung) were performed by log-rank tests. Results: A total of 106 patients were enrolled in this long-term follow-up analysis. At the median follow-up time of 15.32 months (range, 0.97–82.13 months), the median PFS was 6.52 months (95% CI, 5.86–7.14) and the median OS was 15.32 months (95% CI,13.03–17.23). The 12-, 36-, and 60-month OS rates were 61%, 23%, and 15%, respectively. There was a significant difference in OS between cohorts (P = 0.039), with a stronger response observed in lung-treated subgroups. Patients who had received sequential fractions (50 Gy/4f) to the lung had improved OS compared to those who had received sequential fractions (18.29 vs 8.9 months, P = 0.043) to the liver. Subgroup analysis of SABR-targeted lesions showed that lung-targeted groups had significantly longer PFS (6.87 months vs. 5.63 months, P = 0.034) and OS (18.67 months vs. 13.63 months, P = 0.013) compared to liver-targeted groups. The sequence did not affect the outcomes of PFS and OS. Exploratory analyses showed that SABR-targeted lesions and smoking history comprised an independent risk factor for OS. Conclusions: Updated 5-year OS data from the phase II trial demonstrate the long-term clinical benefit of ipilimumab and SABR, which warrants further research and cumulative data.
AB - Purpose: Ipilimumab plus stereotactic ablative radiotherapy (SABR) demonstrate satisfactory short-term clinical benefit and low toxicities in metastatic cancers. Here, we report the 5-year overall survival (OS) rates for patients with metastatic disease treated with this combined-modality therapy in a phase II trial (NCT02239900). Methods and materials: SABR was delivered to patients with metastatic lesions in the liver and lung either during the first dose (concurrent) or 1 week after the second dose (sequential) of ipilimumab (every 3 weeks for 4 cycles). SABR was administered to liver or lung metastases as 50 Gy in 4 fractions or 60 Gy in 10 fractions, considering the tumor location. The OS rates at 12, 36, and 60 months were estimated by the Kaplan-Meier method; subgroup analyses of progression-free survival (PFS) and OS by SABR-targeted lesions (liver/lung) were performed by log-rank tests. Results: A total of 106 patients were enrolled in this long-term follow-up analysis. At the median follow-up time of 15.32 months (range, 0.97–82.13 months), the median PFS was 6.52 months (95% CI, 5.86–7.14) and the median OS was 15.32 months (95% CI,13.03–17.23). The 12-, 36-, and 60-month OS rates were 61%, 23%, and 15%, respectively. There was a significant difference in OS between cohorts (P = 0.039), with a stronger response observed in lung-treated subgroups. Patients who had received sequential fractions (50 Gy/4f) to the lung had improved OS compared to those who had received sequential fractions (18.29 vs 8.9 months, P = 0.043) to the liver. Subgroup analysis of SABR-targeted lesions showed that lung-targeted groups had significantly longer PFS (6.87 months vs. 5.63 months, P = 0.034) and OS (18.67 months vs. 13.63 months, P = 0.013) compared to liver-targeted groups. The sequence did not affect the outcomes of PFS and OS. Exploratory analyses showed that SABR-targeted lesions and smoking history comprised an independent risk factor for OS. Conclusions: Updated 5-year OS data from the phase II trial demonstrate the long-term clinical benefit of ipilimumab and SABR, which warrants further research and cumulative data.
KW - Absolute lymphocyte count (ALC)
KW - Checkpoint inhibitor
KW - Metastasis
KW - Progression-free survival
KW - Radiotherapy
KW - Stereotactic ablative radiotherapy (SABR)
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U2 - 10.1016/j.radonc.2023.109618
DO - 10.1016/j.radonc.2023.109618
M3 - Article
C2 - 36921766
AN - SCOPUS:85150849553
SN - 0167-8140
VL - 183
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
M1 - 109618
ER -