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. 2021 Jul;9(7):e002261.
doi: 10.1136/jitc-2020-002261.

Timing of steroid initiation and response rates to immune checkpoint inhibitors in metastatic cancer

Diana V Maslov  1 , Karine Tawagi  2 , Madhav Kc  3 , Victoria Simenson  4 , Helen Yuan  4 , Cameron Parent  4 , Adi Bamnolker  4 , Richa Goel  4 , Zoe Blake  5 , Marc R Matrana  6 , Daniel H Johnson  6
Affiliations

Timing of steroid initiation and response rates to immune checkpoint inhibitors in metastatic cancer

Diana V Maslov et al. J Immunother Cancer. 2021 Jul.

Abstract

Background: Corticosteroids (CS) are the mainstay of immune-related adverse effect (irAE) management, as well as for other indications in cancer treatment. Previous studies evaluating whether CS affect immune checkpoint inhibitor (CPI) efficacy compared patients receiving CS versus no CS. However, there is a paucity of clinical data evaluating the timing of concomitant CS and CPI efficacy.

Methods: We retrospectively collected data from patients who received CS during CPI treatment at a single institution. Patients were in two cohorts based on timing of initiation of CS (≥2 months vs <2 months after initiating CPI). Patient characteristics, irAEs, cancer type, treatment type, treatment response/progression per RECIST V.1.1, and survival data were collected. Kaplan-Meier and Cox proportional hazard regression methods estimated HRs for the primary endpoint of progression-free survival (PFS) along with overall survival (OS).

Results: We identified 247 patients with metastatic cancer who received CS concurrently with CPIs. The median time on CS was 1.8 months. After adjusting for treatment type, tumor type, brain metastases, and irAEs, those treated with CS ≥2 months after starting CPI had a statistically significant longer PFS (HR=0.30, p<0.001), and OS (HR 0.34, p<0.0001) than those who received CS <2 months after starting CPI. Objective response rate (ORR) for patients on CS ≥2 months was 39.8%, versus ORR for patients <2 months was 14.7% (p value =<0.001) CONCLUSION: Our results suggest that early use of CS during CPI treatment significantly hinders CPI efficacy. This data needs to be validated prospectively. Future studies should focus on the immune mechanisms by which CSs affect T-cell function early in the CPI treatment course.

Keywords: immunotherapy; programmed cell death 1 receptor.

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Conflict of interest statement

Competing interests: There are no competing interests.

Figures

Figure 1
Figure 1
Progression-free survival in those who received CS ≥2 months after initiation of CPI (blue line) versus those who received CS <2 months after initiation of CPI (red line) in total population. CPI, checkpoint inhibitor; CS, corticosteroid; PFS, progression-free survival.
Figure 2
Figure 2
Overall survival in those who received CS ≥2 months after initiation of CPI (blue line) versus those who received CS <2 months after initiation of CPI (red line) in total population. CPI, checkpoint inhibitor; CS, corticosteroid; OS, overall survival.
Figure 3
Figure 3
Progression-free survival in those who received CS ≥2 months after initiation of CPI (blue line) versus those who received CS <2 months after initiation of CPI (red line) in those who were treated with CS for irAEs. CPI, checkpoint inhibitor; CS, corticosteroid; irAE, immune-related adverse effect; PFS, progression-free survival.
Figure 4
Figure 4
Overall survival in those who received CS ≥2 months after initiation of CPI (blue line) versus those who received CS <2 months after initiation of CPI (red line) in those who were treated with CS for irAEs. CPI, checkpoint inhibitor; CS, corticosteroid; irAE, immune-related adverse effect; OS, overall survival.
Figure 5
Figure 5
Progression-free survival in those who received CS ≥2 months after initiation of CPI (blue line) versus those who received CS <2 months after initiation of CPI (red line) in those who were treated with CS for non-irAEs indications. CPI, checkpoint inhibitor; CS, corticosteroid; irAE, immune-related adverse effect; PFS, progression-free survival.
Figure 6
Figure 6
Overall survival in those who received CS ≥2 months after initiation of CPI (blue line) versus those who received CS <2 months after initiation of CPI (red line) in those who were treated with CS for non-irAEs indications. CPI, checkpoint inhibitor; CS, corticosteroid; irAE, immune-related adverse effect; OS, overall survival.
See this image and copyright information in PMC

References

    1. Vaddepally RK, Kharel P, Pandey R, et al. . Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence. Cancers 2020;12:738. 10.3390/cancers12030738 - DOI - PMC - PubMed
    1. Puzanov I, Diab A, Abdallah K, et al. . Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for immunotherapy of cancer (SITC) toxicity management Working group. J Immunother Cancer 2017;5:95. 10.1186/s40425-017-0300-z - DOI - PMC - PubMed
    1. Sgambato A, Casaluce F, Sacco PC, et al. . Anti PD-1 and PDL-1 immunotherapy in the treatment of advanced non- small cell lung cancer (NSCLC): a review on toxicity profile and its management. Curr Drug Saf 2016;11:62–8. 10.2174/1574886311207040289 - DOI - PubMed
    1. Suresh K, Naidoo J, Lin CT, et al. . Immune checkpoint immunotherapy for non-small cell lung cancer: benefits and pulmonary toxicities. Chest 2018;154:1416–23. 10.1016/j.chest.2018.08.1048 - DOI - PMC - PubMed
    1. Tian Y, Abu-Sbeih H, Wang Y. Immune checkpoint Inhibitors-Induced colitis. Adv Exp Med Biol 2018;995:151–7. 10.1007/978-3-030-02505-2_7 - DOI - PubMed