KEY TAKEAWAYS
- The phase II NCI ETCTN study aimed to evaluate the role of ipilimumab in combination with nivolumab for refractory, metastatic SCCA.
- Patients were randomly assigned to nivolumab alone or with or without ipilimumab. PFS was the primary endpoint.
- The study concluded that adding ipilimumab to nivolumab showed a trend towards improved PFS and OS but did not reach statistical significance in refractory SCCA. Increased toxicity was observed with combination therapy.
In a previous single-arm study (NCI9673 Part A), the anti-PD-L1 antibody nivolumab (N) showed promising clinical efficacy in patients with unresectable or metastatic SCCA. In the phase 2 NCI ETCTN study researchers aimed to assess the potential of combining the anti-CTLA-4 antibody ipilimumab (I) with nivolumab for patients with refractory and incurable SCCA.
Patients (pts) who were earlier treated for unresectable or metastatic SCCA naïve to immunotherapy were randomly given (1:1) N (480 mg IV every 4 weeks) alone or with the combination of I (1 mg/kg IV) every 8 weeks. After every 8 weeks (RECIST 1.1), the radiographic response was analyzed. Progression-free survival (PFS) was primary and overall survival (OS), radiographic response rate (RR), and grade ≥3 adverse events (AE’s; CTCAE version 5) were secondary endpoints. Comparison between median PFS between treatment arms one-sided alpha of 0.1 and power of 90% was done with a log-rank test.To estimate the hazard ratio (HR), Cox proportional hazard ratio was utilized.
A total of 100 pts were included in the analysis (52 to N alone; 48 to N + I), after a median follow-up of 21.8 months. The mean age of enrolled pts was 60 years, of which 77% were female.I+ N did not show a statistically significant improvement in PFS (HR .80, 95% confidence interval (CI) .51 – 1.24), with a median PFS of 2.9 months (95% CI, 1.91-3.98) for N alone vs. 3.7 months (95% CI, 2.0-7.1) for N+I (p=0.16). The RR for N and N+I was 17.4% vs. 21.5% (p=.89); 43.5% vs. 47.7% was disease-control rate, and median OS was 15.4 months (95% CI, 11.1-NA) vs. 20.0 months (95% CI, 13.5-23.6; HR .86, 95% CI .51-1.47, p= .59). The 6 pts who received N alone, suffered from Grade ≥3 treatment-related AEs. In contrast, 12 pts who received N+I, one suffered from [grade 5 pneumonitis and two suffered from grade 4 hyperglycemia.The prevalent grade ≥3 treatment-related adverse events were hyperglycemia (4%), pneumonitis (6%), and hyponatremia (5%). The study concluded that adding I to N showed a positive trend in PFS and OS but did not reach statistical significance in refractory, unresectable, or metastatic squamous SCCA pts. However, it resulted in increased toxicity. Ongoing studies aim to further understand the responses to single and combined immunotherapy in this population to guide future study designs.
Source: https://www.annalsofoncology.org/article/S0923-7534(23)00169-2/fulltext
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02314169
V. Morris, K. Ciombor, B. Polite, S. Mukherjee, J. Krauss, A. Shields, O. Aranha, J. Hays, S. Kazmi, B. Weinberg, A. Benson, C. Lieu, S. Iqbal, H. Hochster, L. Xiao, C. Eng, DOI:https://doi.org/10.1016/j.annonc.2023.04.027
