1066P - Negative impact of steroids on the efficacy of immunotherapy in a multi-tumor cohort of patients: time and dose-dependent

Background

Previous data suggest a negative impact of steroids (ST) in patients (pts) treated with immune checkpoint inhibitors (ICI), due to their immunosuppressive properties. How dosage and time of administration modulate this effect is yet to be clarified.

Methods

Retrospective study of pts who received ICI alone in a tertiary university hospital (2016-2022). For each pt, the daily dose of ST was collected (equivalent in mg/kg of prednisone) until progression of disease (PD) or death: 30 days before the 1^st cycle (C1) (-30D), 30 days from C1 (D1-30), 3 months from C1 (D1-90) and after 6 months (m) from C1 (>D6m). We evaluated the impact of the cumulative dose (CD) of ST on the objective response rate (ORR), the disease control rate (DCR) and progression-free survival (PFS).

Results

We evaluated 475 pts (median age: 67.5) with advanced solid tumors (NSCLC: 33.9%; urothelial: 17.3%; renal: 13.7%; melanoma: 11.2%; head and neck: 11.0%; others: 12.9%) treated with anti-PD1 (64.4%), anti-PDL1 (20.4%), anti-PD1 plus anti-CTLA4 (13.3%) or anti-CTLA4 (1.9%); 42.1% in 1^st line, 43.1% in 2^nd line, 14.8% in further lines. Performance status (PS) prior to C1 was: 0 (31.0%), 1 (53.6%), ≥2 (15.4%). 48.2% of pts received ST during therapy with ICI (17.3% in -30D; 32.6% in D1-D90; 16.6% in >D6m). The ORR was significantly lower in pts who received ST in -30D (20.3% [95% CI 11.4-29.1%] vs 36.7% [95% CI 31.8-41.5%]; p<0.01) and in D1-90 (25.7% [95% CI 18.6-32.7%] vs 37.7% [95% CI 32.3-43.1%; p=0.01]). The negative impact of ST was confirmed by a multivariate analysis including PS, type of tumor, disease burden, type of ICI and line of treatment. There was an inverse correlation between the CD of ST in -30D and the DCR (no ST: 52.1%; Q1: 45%; Q2: 30.0%; Q3: 15.8%; Q4: 25%) (p<0.01). The impact of CD was confirmed in D1-30, but not in D1-90 and >D6m. Among pts without PD at 6 months, PFS tended to be longer in those who received ST (23.2 vs 17.6 m; p=0.065).

Conclusions

Our results demonstrate the negative impact of ST on the outcomes of ICI, even at low doses. This effect seems time and dose-dependent, prevailing in pts with an early exposure to ST (<3m) and proportional to cumulative dose only around the initiation of ICI (from -30D to D30).

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Soria Rivas: Financial Interests, Institutional, Advisory Board: MSD, Novartis, Bristol, Roche, Merck, Sanofi Aventis. P. Garrido Lopez: Financial Interests, Institutional, Advisory Board: AstraZeneca, Bristol, Janssen, Lilly, Pfizer, Roche, Novartis, Rovi, Gilead, MSD, Takeda. P. Gajate Borau: Financial Interests, Institutional, Advisory Board: Astellas, Bristol Myers, Ipsen, Merck, Ipsen, Pfizer, Roche. All other authors have declared no conflicts of interest.