The impact of corticosteroid use during anti-PD1 treatment

Abstract

Background The advent of anti-PD1 therapy for cancer treatment has led to improvements in response rates and overall survival. However, anti-PD1 therapy has the potential to cause immune-related adverse events (irAEs), which can be treated with corticosteroids if severe. The clinical implications of concomitant immunotherapy and systemic steroids remain unclear, as short courses of steroids do not significantly suppress T-cell function. The primary objective of this study is to determine if the use of concomitant steroids impacts the efficacy of anti-PD1 therapy. Methods This retrospective, single-center study reviewed adult patients who received at least four cycles of nivolumab or pembrolizumab for the treatment of melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma from November 2014 to February 2016. Patients who received steroids (prednisone equivalent >10 mg) during anti-PD1 therapy were divided into two main cohorts based on the duration of steroid administration of ≤2 weeks or >2 weeks. Time to disease progression, overall response, and overall survival were assessed. Results Twenty-seven of 55 patients (13 melanoma, 11 NSCLC, 3 renal cell carcinoma) required steroids during anti-PD1 therapy. In patients who received steroids, median time to disease progression was 5.6 months for melanoma, 5.8 for NSCLC, and 2.0 for renal cell carcinoma. The overall response rate (ORR) was 3/13 (23%) for melanoma, 6/11 (54%) for NSCLC, and 1/3 (33%) for renal cell carcinoma. Median overall survival was 11.9 months for melanoma, 9.9 for NSCLC, and not reached for renal cell carcinoma. Thirteen patients who had received steroids expired; 11 of these patients had received prednisone >10 mg/day for >2 weeks. Conclusion High-dose steroids for long durations during anti-PD1 therapy may be associated with poorer survival outcomes.

Association of baseline systemic corticosteroid use with overall survival and time to next treatment in patients receiving immune checkpoint inhibitor therapy in real-world US oncology practice for advanced non-small cell lung cancer, melanoma, or urothelial carcinoma

“…CS use during these later CPI treatment periods may have different biological implications and different underlying reasons, such as management of immune-mediated adverse events. 18 , 23 Our findings are consistent with recent reports of clinical outcomes associated with CPI treatment and bCS use in many of the same tumor types, including shorter OS and/or progression-free survival (PFS) in patients who received concomitant CSs with CPI 20 – 22 , 27 , 30 , 38 , 39 – although some differences have emerged in smaller study populations or subgroups, such as those receiving CSs related versus unrelated to cancer care. 24 , 30 , 38 …”

“…Defining the duration of “early” CS use may also be an important factor in interpreting our findings along with those of other recent studies. Although poorer clinical outcomes were observed in patients who received CSs for >2 weeks vs ≤2 weeks, 27 studies that focused on longer time periods – such as 8 weeks 24 or 3 months 30 to define “early” CS use after starting CPI treatment – did not find significant associations. Svaton 41 did not find significant differences for a 2-month period of CS use around CPI treatment, which the authors attributed to a small number of low-dose CS users (22 out of 224 patients).…”

“… 21 Martínez Bernal also reported a significantly worse OS (3 vs 10 months; P = .002) and more progressive disease ( P = .011) in patients with NSCLC receiving ≥20 mg daily prednisone during CPI treatment. 39 In a smaller study of CS use in 27 patients receiving CPIs for aNSCLC, aMel, or renal cell carcinoma and >10 mg/day prednisone equivalent, Pan 27 reported poorer clinical outcomes in patients who received CSs for >2 weeks than in those with shorter courses of CSs (≤2 weeks). 27 In a study of 151 patients with aNSCLC, Fuca and colleagues observed a lower median OS (4.9 vs 15.1 months; P < .001) and PFS (2.0 vs 3.9 months; P = .003) in patients who had CS exposure ≥10 mg daily for ≥1 day during the first 28 days of CPI treatment vs <10 mg per day.…”

“… 39 In a smaller study of CS use in 27 patients receiving CPIs for aNSCLC, aMel, or renal cell carcinoma and >10 mg/day prednisone equivalent, Pan 27 reported poorer clinical outcomes in patients who received CSs for >2 weeks than in those with shorter courses of CSs (≤2 weeks). 27 In a study of 151 patients with aNSCLC, Fuca and colleagues observed a lower median OS (4.9 vs 15.1 months; P < .001) and PFS (2.0 vs 3.9 months; P = .003) in patients who had CS exposure ≥10 mg daily for ≥1 day during the first 28 days of CPI treatment vs <10 mg per day. Corresponding changes were observed at the cellular level, including neutrophil count, neutrophil-to-lymphocyte ratio, and eosinophil count at 4 and 6 weeks after CPI initiation.…”

An update on the safety of nivolumab for the treatment of advanced melanoma

“…Although in the analysis by Weber et all no significant difference in ORRs was found between patients who received systemic corticosteroids due to treatment-related AEs in comparison to those who did not require/received systemic corticosteroids [15], corticosteroids are expected to affect the development of responses (if administered before response) or response duration (if administered after best response). It was primarily shown that long usage of high-dose steroids during anti-PD1 therapy is associated with shorter survival [89].…”