麻豆传媒

Patients who received corticosteroids for palliative reasons drove an overall negative impact of steroids on immunotherapy for advanced non-small cell lung cancer (NSCLC), a retrospective analysis showed.

Patients on prednisone doses of at least 10 mg at the start of anti-PD-1 therapy lived less than half as long as patients treated with lower doses. Progression-free survival (PFS) also was significantly briefer in the 10 mg or more subgroup. However, the overall differences in survival disappeared among patients who received 10 or more mg of prednisone for reasons unrelated to cancer. Only those patients treated palliatively with higher steroid doses had worse overall survival (OS) and PFS.

The results provided some context, following recent reports of worse outcomes among patients treated with higher steroid doses, as reported online in the .

"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," Mark Awad, MD, of Dana-Farber Cancer Institute in Boston, and co-authors concluded. "Additional mechanistic studies are needed to identify whether the use of corticosteroids affects specific aspects of the immune system necessary for immunotherapy activity."

The data are consistent with clinical opinions about corticosteroids and their immunosuppressive effects in patients with cancer, but do not necessarily resolve the issues, according to David Graham, MD, of the Atrium Health Levine Cancer Institute in Charlotte, North Carolina.

"Since immunotherapies are meant to allow the immune system to attack the tumor, we have worried that corticosteroids, which can suppress the immune system, may interfere with their activity," said Graham, who is an American Society of Clinical Oncology expert. "This study may add credence to that idea but seems to more suggest that patients who need higher levels of steroids (more than 10 mg prednisone daily) are sicker and have poorer outcomes because of that fact."

"We have long known that sicker patients, particularly exhibited by an ECOG performance status of 2 or more, have poorer outcomes," he continued. "This fits in with that idea. If a patient is sick enough that they need more than 10 mg prednisone daily, immunotherapy may not be the best choice for them."

It "would make sense" that the findings might apply to immunotherapy for other types of cancer, but that has not been shown, he added. "I would use them in any patient with a need for significant steroid use with great caution and with a full discussion with the patient."

Corticosteroids are widely used in the treatment of patients with cancer, including palliative and nonpalliative indications. With the advent of immune checkpoint inhibitors and other forms of immunotherapy for cancer, some concern arose over the possibility that concomitant steroid therapy might blunt the anticancer activity of immunotherapies. Two recent studies involving patients with NSCLC supported that concern, one showing worse outcomes in patients who received at least 10 mg of prednisone along with different PD-1/L1 inhibitors and limited to patients treated with nivolumab (Opdivo).

In an effort to add granularity to the data, Awad and co-authors retrospectively analyzed data for patients who received a PD-1 or PD-L1 inhibitor for NSCLC from July 2011 to September 2018. The team excluded patients who received chemotherapy in addition to a PD-1/L1 inhibitor.

The study focused on outcomes in three groups of patients:

• Those on 10 or more mg prednisone for cancer-related palliative indications at the start of immunotherapy

• Patients who received 10 or more mg of prednisone during immunotherapy for nonpalliative indications (such as autoimmune disease or hypersensitivity reactions)

• Patients who received less than 10 mg prednisone at the start of immunotherapy

The analysis included 650 patients, 93 (14.3%) of whom received at least 10 mg of prednisone within 24 hours of initiating immunotherapy. The group included 66 patients who received corticosteroids for palliative indications, primarily brain metastases (57.6%), cancer-related dyspnea (18.2%), and cancer-related bone pain (16.7%). Most of the remaining 27 patients received corticosteroids for radiation- or chemotherapy-related pneumonitis, chronic obstructive pulmonary disease, autoimmune disease, or iodinated contrast prophylaxis.

An analysis of clinical outcomes by indication for corticosteroids showed that patients who received at least 10 mg prednisone had lower objective response rates (10.8% vs 19.7%, P=0.04), shorter median PFS (2.0 vs 3.4 months, P=0.01), and shorter median OS (4.9 vs 11.2 months, P<0.001) as compared with patients who received lower doses of prednisone (including none).

Patients who received higher doses of prednisone for palliative indications had significantly worse outcomes as compared with patients who received 10 or more mg prednisone for nonpalliative indications or who received lower doses: objective response (6.1% vs 22.2% vs 19.7%, P=0.01), PFS (1.4 vs 4.6 vs 3.4 months, P<0.001), and OS (2.2 vs 10.7 vs 11.2 months, P<0.001).

Patients who received 10 or more mg prednisone for nonpalliative indications had response rates, PFS, and OS that did not differ significantly from patients who received less than 10 mg.

The authors noted that their findings are consistent with those of two recent studies of patients with advanced NSCLC treated with pembrolizumab (Keytruda) and or .

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