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Steroid Use May Blunt Anti-PD-1 Effect in NSCLC

— Lower response rate, PFS, survival with ≥10 mg/day baseline dose

Last Updated August 30, 2018
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Patients who received a steroid dose ≥10 mg/day prior to starting anti-PD-1/PD-L1 therapy for non-small cell lung cancer (NSCLC) had significantly worse outcomes, a large retrospective study showed.

The threshold baseline steroid dose was associated with a 30% increase in the risk of disease progression or death and a 70% increase in the survival hazard, as compared with patients who received lower steroid doses or no steroids prior to starting an one of the immune checkpoint inhibitors.

The "real-world" data addressed an issue avoided by major clinical trials of PD-1/PD-L1 inhibitors, which typically excluded patients with a history of steroid use at enrollment, reported Matthew D. Hellmann, MD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York City, and colleagues in the .

"Treatment with PD-(L)1 blockade has been a significant advance for patients with NSCLC and other malignancies," they wrote. "As these agents have become a standard of care, it is imperative that we recognize and inform common practices that may affect the efficacy of these agents."

The findings provided data to support a lingering clinical suspicion regarding the use of steroids, David L. Graham, MD, an expert for the American Society of Clinical Oncology, said in a statement.

"We often prescribe steroids to help alleviate the side effects of cancer and its treatment, particularly in non-small cell lung cancer," said Graham, of the Levine Cancer Institute in Charlotte, North Carolina. "However, there have been concerns that steroid use may negatively impact the efficacy of immunotherapies, which are now the standard of care for many patients with NSCLC."

"This study represents a step toward affirming that general consensus, but more research is needed to confirm the impact of steroids in patients with advanced cancer treated with checkpoint inhibitors as a single agent," he added.

As Graham noted, steroids are widely used to manage adverse effects of cancer and treatment, particularly in patients with advanced NSCLC. Indications for steroids include fatigue, dyspnea, decreased appetite, and symptomatic brain metastases.

The immunosuppressive properties of corticosteroids and potential effect on T-cell function have led to concern about steroids interfering with the activity of immune checkpoint inhibitors, including anti-PD-1/PD-L1 drugs. Consequently, pretreatment steroid use has been a uniform exclusion factor in clinical trials of immune checkpoint inhibitors, Hellmann's group noted. Reassuring data have emerged from studies of to manage immune-mediated adverse events.

To examine the impact of baseline steroid therapy on anti-PD-1/PD-L1 efficacy in NSCLC, the authors reviewed records of patients from two institutions: MSKCC and Gustave Roussy Cancer Center in Villejuif, France. The analysis comprised a total of 640 patients, 445 from MSKCC and 185 from Gustave Roussy. The patients initiated single-agent treatment with a PD-1/PD-L1 inhibitor in clinical oncology practice, outside a clinical trial.

The authors identified 90 (14%) patients with advanced NSCLC who had a corticosteroid dose ≥10 mg/day at the start of immune checkpoint inhibitor therapy. An additional 17 (3%) patients had baseline steroid use <10 mg/day, which was considered within the range of normal adrenal replacement and not a typical exclusion from clinical trials. Indications for corticosteroids included dyspnea (33%), fatigue (21%), and brain metastases (19%).

In the MSKCC cohort, baseline corticosteroid use ≥10 mg/day was associated with a significantly lower response rate (6% versus 19%, P=0.02), median progression-free survival (PFS) at 1.9 versus 2.6 months (P=0.001), and overall survival (OS) at 5.4 versus 12.1 months (P<0.001). In the French cohort, response rate was lower in the patients with baseline steroid use ≥10 mg/day but not significantly so (8% versus 18%, P=0.2). PFS was modestly but significantly lower (1.7 versus 1.8 months, P<0.001), and OS was almost three times lower (3.3 versus 9.4 months, P<0.001).

In the pooled analysis of all 640 patients, baseline corticosteroid use ≥10 mg/day had a significant association with lower PFS (HR 1.3, P=0.03) and OS (HR 1.7, P<0.001), the authors stated.

The study had some limitations including the small number of patients who received corticosteroids of any dose at the time of immune checkpoint blockade (ICB) initiation. This "which may reflect the caution of clinical providers in administering corticosteroids to patients being treated with ICB," Hellmann's group pointed out.

  • author['full_name']

    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined 鶹ý in 2007.

Disclosures

Hellmann disclosed relevant relationships with Bristol-Myers Squibb, Merck, Genentech, AstraZeneca, MedImmune, Janssen Pharmaceuticals, Mirati Therapeutics, Syndax, and Shattux Labs.

Primary Source

Journal of Clinical Oncology

Arbour KC, et al "Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non-small cell lung cancer" J Clin Oncol 2018; DOI:10.1200/JCO.2018.79.0006.