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03-07-2019 | Oncology | News | Article

Steroid indication plays key role in link to poor immunotherapy outcome

medwireNews: Poor outcomes among patients with non-small-cell lung cancer (NSCLC) who receive corticosteroids prior to immunotherapy are driven by the use of steroids for palliative oncologic symptom management, study findings indicate.

As previously reported by medwireNews, use of 10 mg/day or higher doses of prednisone before initiation of immune checkpoint inhibitor (ICI) therapy has been associated with poor outcomes in patients with NSCLC.

However, Mark Awad (Dana-Farer Cancer Institute, Boston, Massachusetts, USA) and colleagues note that corticosteroids are commonly used to treat cachexia, fatigue, and other cancer-related symptoms associated with a poor prognosis and therefore shorter survival “may not necessarily be a result of a corticosteroid-related blunting of the antitumor immune response to ICIs.”

To investigate “the question of causation versus correlation for this association,” they analyzed data for 650 ICI-treated patients with advanced NSCLC according to the indication for corticosteroid use.

Overall, 93 (14.3%) patients were taking prednisone at a dose of at least 10 mg/day at the time of immunotherapy initiation, and these patients had a significantly lower objective response rate (ORR) than patients who received a lower prednisone dose, 10.8% versus 19.7%.

They also had significantly shorter median progression-free survival (PFS; 2.0 vs 3.4 months) and overall survival (OS; 4.9 vs 11.2 months).

But the researchers report in the Journal of Clinical Oncology that the difference was driven by a “poor-prognosis subgroup of patients who receive corticosteroids for palliative indications.”

Specifically, the ORR was significantly lower for the 66 patients who received 10 mg/day or more of prednisone for palliative cancer reasons than among the 27 patients who received the same dose of the corticosteroid for other indications, at 6.1% versus 22.2%.

Median PFS (1.4 vs 4.6 months) and OS (2.2 vs 10.7 months) were also significantly worse among patients in the higher-dose palliative care group than in the higher-dose non-palliative care group.

Furthermore, there was no significant difference in median PFS or OS between patients receiving 10 mg/day or more of prednisone for non-cancer reasons and those receiving a lower dose of prednisone regardless of the reason.

And after adjustments for potential confounders, the use of 10 mg/day or more of prednisone for cancer-related indications was associated with a significant 60% increased risk for death relative to the use of a lower dose for any reason.

“In conclusion, our data suggest that corticosteroids should not necessarily be decreased or discontinued before the start of immunotherapy out of a theoretical concern that corticosteroids could impair a response to immunotherapy,” Awad et al remark.

They add: “Additional mechanistic studies are needed to identify whether the use of corticosteroids affects specific aspects of the immune system necessary for immunotherapy activity.”

By Laura Cowen

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

J Clin Oncol 2019; doi:10.1200/JCO.19.00189

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