‘Poor Outcomes’ for Patients With Lung Cancer, Diabetes on Keytruda

“Diabetes might reduce the efficacy of immunotherapy,” co-author Dr. Yasmin Leshem, said.

Immunotherapy treatment with Keytruda (pembrolizumab) is not as effective or beneficial for patients with both metastatic non-small cell lung cancer (NSCLC) and preexisting diabetes mellitus (DM), researchers have found.

A humanized antibody used in cancer immunotherapy, Keytruda is typically used to treat patients with NSCLC. However, a recent study published in Cancer found that overall survival (OS, the time after treatment that a patient is still alive) for patients with both NSCLC and DM was shorter when treated with Keytruda alone compared to when taken with chemotherapy.

“Diabetes might reduce the efficacy of immunotherapy,” co-author Dr. Yasmin Leshem, a medical oncologist at the Tel Aviv Sourasky Medical Center in Israel, told CURE via email. “If our findings will be further validated, the next step will be to find ways to mitigate this effect and prolong patients' survival.”

In the study’s cohort of 203 eligible patients with NSCLC receiving first-line Keytruda, 51 (25%) had both metastatic NSCLC and preexisting DM, and the mean age was 73 for patients with DM. From the 51 patients, seven (14%) were treated with insulin, as most of the patients had type 2 DM. The authors noted that prior studies confirmed diabetes and poor glycemic control had compromised efficacy when chemotherapy was involved.

Findings from the current study emphasized that differences in outcomes depended on treatments and treatment combinations. The authors established that patients who received a combination of Keytruda and chemotherapy had a better overall survival than patients who received only pembrolizumab.

“The difference in survival of patients with DM to those that did not have DM was more pronounced in the cohort of those receiving (Keytruda) alone (12 months for patients with DM vs. 27 months for patients without DM) compared to patients receiving chemo-pembrolizumab (14.3 months vs. 19.4 months),” said Leshem. “It is possible that the detrimental effect of DM on treatment is more pronounced on therapies that rely solely on immunotherapy.”

This result was because chemotherapy could offset some of the harmful effects of DM. According to the authors, immunotherapies like Keytruda modify the body and indirectly influence cancer cells. In that sense, the authors suggested that DM hindered a host’s capability to produce efficient antitumor immunity.

The rate of progression-free survival (PFS) — the period during and after treatment of cancer when the disease does not get worse — also varied among patients with NSCLC and DM compared with patients without DM, the authors found. The study determined that the presence of DM significantly reduced the PFS, in which the risk of disease progression was 67% higher than patients who were nondiabetic. Furthermore, the authors found that the presence of DM negatively affected the OS; patients with NSCLC and DM had a risk of death that was 73% higher than patients without DM.

“Our study point(ed) to an unknown association between poor outcomes in NSCLC patients receiving pembrolizumab and (had) preexisting diabetes,” Leshem said. “While we still do not know the full impact of this association, it will be prudent for patients to make an effort to reach good glycemic control while receiving pembrolizumab or other immunotherapy drugs.We hope more research will follow and broaden our knowledge regarding the connection between DM and immunotherapy.”

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