Pembrolizumab is less effective in people with diabetes

the essentials in brief

Ask: Does diabetes affect the effectiveness of first-line immunotherapy with pembrolizumab with or without chemotherapy in people with NSCLC?

Answer: People with diabetes have significantly shorter median progression-free and overall survival with pembrolizumab.

Meaning: The study suggests that immunotherapy is less beneficial in diabetic NSCLC patients.

Limitation: The study is limited by its retrospective nature.

Tel Aviv. Although it is known that people with diabetes often have weakened immune systems, it is unclear whether the disease affects the effectiveness of immunotherapy. According to a study from Israel (Cancer 2023; online June 24th), that seems to be the case. In patients with metastatic NSCLC who received pembrolizumab as first-line therapy, diabetes was associated with significantly shorter progression-free and overall survival.

A team led by Dr. Yasmin Leshem of the Tel Aviv Sourasky Medical Center in Tel Aviv examined medical records of 203 people with metastatic NSCLC. They received pembrolizumab as first-line therapy with or without chemotherapy in a single center. 25 percent of participants also had diabetes. 82 percent of them were taking oral antidiabetic drugs, most (63 percent) taking metformin. 14 percent received insulin and another 14 percent received no diabetes treatment at all. For validation, the researchers used data from the state health organization Maccabi Healthcare Services.

Overall survival of 12 vs. 21 months

Nearly 27 months of follow-up found that people with diabetes had a significantly shorter median progression-free survival (PFS) than non-diabetics (5.9 vs. 7.1 months). The median overall survival (OS) was also significantly shorter (12.0 vs. 21.0 months).

The difference in OS was more pronounced in people with diabetes treated with pembrolizumab alone (12.0 vs. 27.0 months) than in those with additional chemotherapy (14.3 vs. 19.4 months).

“It therefore appears that chemotherapy can counteract some of the harmful effects of diabetes,” said Leshem and team.

Diabetes as an independent risk factor

A multivariate analysis suggested that diabetes is an independent risk factor for a shorter PFS and OS; the risk of this was significantly increased by 67 percent and 73 percent, respectively, in those affected.

Data from a validation cohort of 452 patients and patients with metastatic NSCLC showed that treatment with pembrolizumab was shorter in people with diabetes than in people without diabetes. The proportion who continued this therapy after twelve months was 19.6 percent among people with diabetes and 31.7 percent among those without diabetes.

Is anti-tumor immunity compromised?

“Unlike other treatment methods, including chemotherapy and targeted therapy, immunotherapy modifies the host and only indirectly affects the cancer cells,” says Leshem’s research team. The results suggested the possibility that diabetes could impair the ability to build effective antitumor immunity.

“The data indicate that immunotherapy is less beneficial in diabetic NSCLC patients,” conclude Leshem and colleagues. Further studies are needed to validate the results and examine similar effects in other types of cancer.

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