Addition of Tiragolumab to Tecentriq-Chemo Combo Fails to Boost Outcomes in Small Cell Lung Cancer

Survival outcomes and side effect rates were similar in patients with extensive-stage small cell lung cancer who did and did not have tiragolumab added to their treatment regimen of Tecentriq and chemotherapy.

Patients with previously untreated extensive-stage small cell lung cancer did not achieve improved outcomes when tiragolumab was added to a regimen of Tecentriq (atezolizumab) plus carboplatin and etoposide (a chemotherapy duo referred to as CE), according to findings from the phase 3 SKYSCRAPER-02 clinical trial.

“The vast majority of patients with extensive-stage small cell lung cancer continue to suffer disease progression, with a median of about 5.5 months from the time of diagnosis. So there’s clearly a major unmet need for the treatment of these patients,” study author Dr. Charles M. Rudin, chief of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center in New York City, said while presenting the findings at the 2022 American Society of Clinical Oncology Annual Meeting.

A total of 490 patients were involved in the trial: 243 were randomly assigned to receive tiragolumab, Tecentriq and CE, while 247 were assigned to receive placebo plus Tecentriq and CE. The main goals of the study were progression-free survival (time from treatment until disease worsens) and overall survival (time from treatment until death from any cause) in a group of patients who did not have brain metastases at the start of the study.

Secondary endpoints of the study were progression-free survival and overall survival in the whole patient population, including those with brain metastases.

“Brain metastases were present in about 19% of the patients on both arms at diagnosis, and about two-thirds of these were untreated at the time they started on systemic therapy,” Rudin said.

As of February 2022, the average progression-free survival was 5.4 months in the tiragolumab-containing regimen, compared with 5.6 months in placebo group in the patients enrolled in the study without the history of or had brain metastases at baseline.

Average progression-free survival was 5.1 months and 5.4 months in the tiragolumab and placebo groups, respectively.

For those with brain metastases, average overall survival was 13.6 months in both the tiragolumab and non- tiragolumab groups, while overall survival in the entire patient population was 13.1 months for patients in the tiragolumab group and 12.9 months in the placebo group.

“I think I can summarize these (findings) by saying there doesn’t appear to be any subgroup that selectively benefits from the addition of tiragolumab,” Rudin said. “All of the confidence intervals overlap.”

More than half (52.3%) of patients in the tiragolumab group experienced severe side effects. Similarly, 55.7% in the placebo group experienced severe side effects.

A total of 5% and 5.3% of patients in the tiragolumab and placebo groups, respectively, had side effects that led to stopping treatment.

“We saw what we expected to see in terms of toxicity of the chemotherapy backbone and (Tecentriq. There’s )really not much difference in terms of safety signals between the two arms,” Rudin said.

The data presented at the meeting are an extension of the preliminary findings of the trial that were released by the drug’s manufacturer, Roche, in March. At the time, the preliminary findings showed that the anti-TIGIT immunotherapy tiragolumab plus the Tecentriq-chemotherapy combo failed to elicit a survival benefit in this patient population.

Ultimately, the lack of benefit seen with the addition of tiragolumab on the SKYSCRAPER-02 trial mimic results previously seen on the EMPOWER-3 trial, according to Rudin.

“From a clinical standpoint, based on these data, our conclusion is that targeting TIGIT in extensive-stage small-cell lung cancer does not appear to be therapeutically relevant,” he concluded. “We’re continuing to follow these folks and biomarker analyses will be forthcoming. I think those will be interesting in informing us about the subgroups that benefits from immunotherapy.”

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