The article by Kapoor et al. and the accompanying editorial highlight the important issue of the usage of corticosteroids along with immunotherapy in advanced cancers.[12]
The use of steroids with immunotherapy is inevitable in certain situations. With the approval of immunotherapy combined with chemotherapy as the best first-line option in advanced non-small cell lung cancer, the use of steroids as antiemetics becomes necessary. Similarly, with around 20% of patients presenting with brain metastasis, steroids form an integral part of treatment and their concurrent use with immunotherapy may be unavoidable.
It is a difficult question to answer, whether the use of steroids actually jeopardizes the efficacy of immunotherapy or selects out a group of patients with poor prognosis (brain metastases) or more aggressive disease who will not have any benefit with immunotherapy.
Banna et al. developed a tool for choosing between immunotherapy and chemotherapy in lung cancer and listed performance status ≧1, high neutrophil-to-lymphocyte ratio, and high-dose corticosteroids as unfavorable for immunotherapy.[3] Very recent data in a larger subset of patients using corticosteroids and immunotherapy were presented as an abstract at ESMO 2019.[4] A total of 146 patients received corticosteroids (the largest number thus far compared to other studies), and it was seen that the overall survival (OS) was longer in the group that did not receive steroids or <10 mg of steroids (14.7 vs. 8.3 months). However, there was no difference in progression-free survival. On multivariate analysis, the use of steroids was identified as an independent variable for poorer outcomes. The study also looked at the role of antibiotics affecting the efficacy of immunotherapy, and no significant correlation was found, with comparable OS. This is in opposition to the findings of Kapoor et al.,[1] which may be explained by the fact that the former study had many more patients (141) who received antibiotics versus fewer number of patients (27) in the latter study. However, how many out of these 141 patients received both steroids and antibiotics is not detailed in the abstract. The timing of antibiotics is also crucial as a recent study showed that antibiotic therapy administered before immunotherapy, not concurrently, was associated with worse response to treatment and OS.[5]
The studies discussed in the article by Kapoor et al. largely show a negative impact of steroids. The latest study from Europe also walks the same path although it may be due to the steroids selecting out patients with larger volume and more aggressive tumors. One must be prudent while using steroids with immunotherapy, and a risk–benefit assessment is essential before their use, especially in emergency situations such as brain metastases, where steroid use is unavoidable.
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Conflicts of interest
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REFERENCES
1. Kapoor A, Noronha V, Patil VM, Joshi A. Concomitant use of corticosteroids and immune checkpoint inhibitors in patients with solid neoplasms: A real-world experience from a tertiary cancer center Cancer Res. 2019;2:204–8
2. Rangarajan B, Abhinav RK. Beyond the tumor and tumor milieu – Factors affecting responses to immunotherapy Cancer Res Stat Treat. 2019;2:224
3. Banna GL, Passiglia F, Colonese F, Canova S, Menis J, Addeo A, et al Immune-checkpoint inhibitors in non-small cell lung cancer: A tool to improve patients' selection Crit Rev Oncol Hematol. 2018;129:27–39
4. Martinez JM, Riuvadets M, Garcia-Campelo M, Lopez JS, Palacios GA, Melo PG, et al Impact of corticosteroids and antibiotics on efficacy of immune-checkpoint inhibitors in advanced non-small cell lung cancer Ann Oncol. 2019;30(Suppl 5):v475–v532
5. Pinato DJ, Howlett S, Ottaviani D, Urus H, Patel A, Mineo T, et al Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer JAMA Oncol. 2019;5:1774–8
