The new phase III clinical trial demonstrated that adding the immunotherapy drug pembrolizumab to chemotherapy doubled survival in people with metastatic nonsquamous non-small cell lung cancer (NSCLC) and no mutations in the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) gene.
The results of the trial, which took place in more than a dozen countries, are now published in the New England Journal of Medicine.
The study also featured at the recent annual meeting of the American Association for Cancer Research in Chicago, IL.
"The data show," explains lead study author Prof. Leena Gandhi, the director of the Thoracic Medical Oncology Program at NYU Langone Health in New York City, "that treatment with pembrolizumab and chemotherapy together is more effective than chemotherapy alone."
Prof. Gandhi notes that, in addition to chemotherapy, some groups of NSCLC patients benefit from immunotherapy drugs that boost their natural anti-cancer defenses, and targeted therapy that prevents mutations in genes such as EGFR and ALK from aiding the cancer.
However, for over 30 years, chemotherapy alone has been the "standard treatment" for those who have nonsquamous NSCLC without mutated EGFR or ALK genes.
The results of the study could pave the way to a "new standard of care" for this group, she adds.
An aggressive lung cancer
Lung cancer is the second most frequently diagnosed cancer type and the primary cause of cancer deaths in the United States.
Around 80–85 percent of lung cancers are NSCLC, of which there are several subtypes. Of these, nonsquamous NSCLC accounts for 70–75 percent of cases.
In most cases of NSCLC, by the time the disease is diagnosed, it has already reached metastasis — that is, the stage at which the cancer has invaded nearby tissue or spread to other parts of the body.
This is the main reason that survival rates in diagnosed NSCLC are poor compared with many other cancers.
Pembrolizumab combined with chemotherapy has already been approved in the U.S. to treat this group of patients. The approval was granted following a phase II trial that was co-led by Prof. Gandhi.
Combined therapies doubled survival rates
In the newly reported phase III trial, the researchers randomly recruited 616 people with metastatic nonsquamous NSCLC, from 118 sites in over a dozen countries.
They randomly assigned the participants — in a ratio of 2:1 — to receive either pembrolizumab and the standard chemotherapy (405 participants), or the standard chemotherapy and a placebo (202 participants).
The standard chemotherapy consisted of a platinum-based drug with "pemetrexed maintenance therapy."
None of the participants had been treated for their cancer before they joined the trial, and none had mutations in their EGFR or ALK genes, and so could not qualify for targeted therapy.
They found that, in addition to improved response rates, rates of "overall and progression-free survival" were greater in the group that received standard chemotherapy with pembrolizumab.
The chance of disease progression or death in those who had chemotherapy with pembrolizumab was 48 percent less than those who received chemotherapy with placebo.
This suggests that adding the immunotherapy drug to the platinum-based standard chemotherapy just about doubled overall and progression-free survival.
"Using this combination therapy to treat patients with such an aggressive disease could be an important advance in keeping patients alive and well for longer."
Prof. Leena Gandhi
The overall chances of adverse effects were about the same in both groups: it was 67.2 percent in the chemotherapy with pembrolizumab group, and it was 65.8 percent in the chemotherapy with placebo group.
The most common adverse effects in both groups were anemia, nausea, and fatigue. But there was a higher chance of developing "kidney injury" in the chemotherapy with pembrolizumab group (5.2 percent) than in the chemotherapy with placebo group (0.5 percent).
The trial was supported by Merck, and some employees of the drug company were involved in the analysis of results, the review, and writing of the report. Another drug company, Eli Lilly, supplied the pemetrexed.