KEY TAKEAWAYS
- Insights from this study could lead to new and better treatments for recurrent/metastatic SGC. The study combined Nivolumab and Ipilimumab with hypofractionated radiation for these patients.
- The primary endpoint was safety and tolerability, while the secondary endpoints were objective response rates, overall survival, and progression-free survival.
- The most common grade 3 AEs were adrenal insufficiency, hypokalemia, lung infection, hypotension, and mania. No grade 4/5 toxicities were observed.
No standard systemic therapy exists for recurrent/metastatic salivary gland cancers (SGCs). Immune checkpoint inhibitors (ICIs) exhibit limited effectiveness in SGC treatment. Preclinical studies in solid tumors suggest synergistic antitumor effects with ICIs and hypofractionated radiotherapy (XRT). The study explored the safety and efficacy of nivolumab (N) and ipilimumab (I) combined with palliative XRT.
In this phase I/II open-label single-arm trial, patients with incurable SGCs (WHO 2017), evidencing progression, ECOG status 0-1, and no prior anti-PD1 or CTLA4 therapy, patients received N every 2 weeks for 12 doses (480 mg), followed by every 4 weeks for 8 doses. I was administered every 6 weeks for 4 doses. Disease assessment was based on RECIST 1.1 criteria. Hypofractionated XRT at 24 Gy in 3 fractions every other day over 1 week started 2 weeks after the initial doses of N and I. Research blood collection occurred before weeks 1, 8, and 16.
The primary endpoint involved evaluating safety and tolerability using CTCAE v. 4. Secondary endpoints encompass assessing objective response rates (ORR) based on RECIST 1.1 criteria in non-irradiated sites of measurable disease, overall survival (OS), and progression-free survival (PFS). The study, with approval from the FHCC IRB.
A total of 20 patients were enrolled between 4/2019 and 5/2022, with a median age of 58 (range 27-77) years, where 50% were male, 60% had ECOG 0, and 35% were Asian. The most common histologies were adenoid cystic (45%) and salivary duct (20%), 75%) had no prior systemic therapy. Half (50%) had both local and distant disease, and 70% had commercial NGS testing, all showing TMB < 10mut/Mb and MSI-stable tumors. All patients completed XRT, with the lung as the most common XRT site (65%) and bone (35%). The median number of N doses received was 12 (range 3-20), and I doses were 4 (range 1-4). Enrollment was halted until the first 6 patients were assessed for dose-limiting toxicities during the initial 12 weeks of treatment, with none observed.
Among all enrolled patients, 20% experienced Grade 3 adverse events (AEs): adrenal insufficiency, hypokalemia, lung infection, hypotension, and mania. No Grade 4/5 toxicities were observed. One patient was not evaluable for RECIST 1.1 due to rapid disease progression. 20% showed partial responses (2 pts salivary duct, 1 acinic cell, 1 adenoid cystic) lasting a median of 15.5 months (range 6-16 mos), 30% had stable disease for 6 mos or more, and 45% had progressive disease. With a median follow-up of 16 mos, the median OS was 25 mos (95% CI: [1.56, 2.59]), and the median PFS was 7.2 mos (95% CI: [0.21, 1.56]). Exploratory correlative peripheral blood analysis was ongoing and will be reported.
Nivolumab/ipilimumab with palliative XRT showed low toxicity, modest ORR, and durable ORR/SD, requiring further study of response predictors.
Source: https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.6011
Clinical Trial: https://www.clinicaltrials.gov/study/NCT03749460
Cristina P. Rodriguez, Vicky Wu, Kevin Ng, Jenna M. Voutsinas, Ariana Dumenigo-Jimenez, Jonathan R. Fromm, Renato G. Martins, Keith D. Eaton, Rafael Santana-Davila, Christina S Baik, Sylvia Lee, Diane Tseng, Neal D. Futran, Brittany Barber, Emily Marchiano, Jeffrey Houlton, George E. Laramore, Jay Justin Liao, Simon S. Lo, Upendra Parvathaneni. DOI 10.1200/JCO.2023.41.16_suppl.6011, J Clin Oncol 41, 2023 (suppl 16; abstr 6011).
