Treatment with the anti-TIGIT antibody vibostolimab and Keytruda (pembrolizumab) plus etoposide and platinum did not improve overall survival versus Tecentriq (atezolizumab) plus etoposide and platinum in patients with extensive-stage small cell lung cancer (SCLC), according to data from a phase 3 trial presented at the 2024 SITC Annual Meeting.
As frontline therapy, the investigational regimen led to a median overall survival of 11.5 months versus 12.9 months with the control regimen. Median progression-free survival was 5.3 months versus 4.5 months, respectively.
“Based on the benefit/risk profile observed, treatment with vibostolimab/[Keytruda] was discontinued in the KEYVIBE-008 trial,” Dr. Jacob Sands, lead study author, assistant professor at Harvard Medical School, and Oncology Medical Director of the International Patient Center at Dana-Farber Cancer Institute in Boston, said in a presentation of the data. “Investigation of vibostolimab/[Keytruda] is ongoing in non–small cell lung cancer [NSCLC].”
The announcement of the trial’s discontinuation was first made in August 2024 in accordance with the recommendation from an independent data monitoring committee.
Glossary:
Anti-TIGIT antibody: a type of immunotherapy that targets the protein, TIGIT, found on immune cells.
Frontline therapy: the first course of treatment used to treat a disease.
Partial response: a decrease in tumor size or extent of cancer throughout the body.
Objective response rate: percentage of patients with a partial or complete response from treatment.
Duration of response: the time from the start of treatment until when the disease progresses, or the patient dies.
Overall survival: the time when a patient with cancer is still alive.
Progression-free survival: the time when a patient with cancer lives without disease worsening.
Leukopenia: lower-than-normal number of leukocytes, a type of white blood cell.
Metastatic: spreading of disease.
Additional efficacy results revealed that the six- and 12-month overall survival rates with the investigational regimen were 78.7% and 49.1%, respectively, and 87.4% and 55%, respectively, with the control regimen. The six- and 12-month progression-free survival rates in the investigational group were 30% and 12.4%, respectively, and 26.5% and 13.3%, respectively, in the control group.
The objective response rate was 71.7% in the investigational group versus 74.8% in the control group. The median duration of response was 4.2 months with vibostolimab/Keytruda versus 3.9 months with Tecentriq. In the investigational group, best responses included complete response (6.1%), partial response (65.7%), stable disease (15.7%) and progressive disease (4.8%). In the control group, best responses included complete response (6.1%), partial response (68.7%), stable disease (13.5%) and progressive disease (5.2%).
Despite the trial’s results, there had been substantial evidence in support of the regimen’s potential efficacy, including findings from the phase 3 KEYNOTE-604 trial. These findings showed improved progression-free survival, though not overall survival, with the first line of therapy combination of Keytruda and etoposide and platinum in SCLC.
“Grade 3 or greater [treatment-related side effects] and immune-mediated [side effects] were more frequent with vibostolimab/Keytruda versus [Tecentriq], consistent with dual immune checkpoint inhibitor therapy,” Sands said. He added that no new safety signals were identified.
Common treatment-related side effects in the investigational group were anemia, low white blood cell count, leukopenia, hair loss, low platelet count, nausea, decreased appetite, constipation, fatigue, weakness, rash and itching.
Immune-mediated side effects and infusion reactions included underactive thyroid, overactive thyroid, infusion reactions, lung inflammation, inflammation of the pancreas, adrenal insufficiency, inflammation of colon, severe skin reactions, type 1 diabetes, inflammation of the pituitary gland, brain inflammation, hepatitis and stomach inflammation.
The median duration of therapy was 4.9 months in the investigational group versus 4.9 months in the control group. Most treatment-related side effects were between grade 3 (severe) and 5 (deadly) in the investigational (66.8%) and control (57.2%) groups. Treatment-related side effects leading to discontinuation of any treatment or death occurred in 11.8% and 1.7% of patients, respectively, in the investigational group, and 6.6% and 0.9%, respectively, of patients in the control group. Severe, life-threatening, or death causing immune-mediated side effects and infusion reactions occurred in 14.8% of patients in the investigational group versus 3.5% in the control group; 0.9% of events led to death in the investigational group.
KEYVIBE-008 was a trial that enrolled patients at least 18 years of age with newly diagnosed, previously untreated extensive-stage SCLC and measurable disease.
In the investigational group the median patient age was 64 years and 67% of patients were men. Most patients were current or former smokers (91.7%). The majority of patients also had stage 4B disease (60%), lactate dehydrogenase above the upper limit of normal (60%) and at least three metastatic sites (78.3%). Median tumor size was 142 millimeters.
The median time from treatment assignment to data cutoff was 16.6 months. Of the 230 patients who had been randomly assigned, 229 started treatments in each group. At data cutoff, 16 patients in the investigational group and 29 in the control group were in ongoing treatment.
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