medwireNews: Adding tiragolumab to atezolizumab plus carboplatin and etoposide provides no additional progression-free (PFS) or overall survival (OS) benefit to patients with untreated extensive-stage small-cell lung cancer (ES-SCLC), phase 3 study data show.
Furthermore, the findings of the SKYSCRAPER-02 trial, presented at the 2022 ASCO Annual Meeting in Chicago, Illinois, USA, were consistent regardless of brain metastasis status.
Charles Rudin, from the Memorial Sloan Kettering Cancer Center in New York, USA, said that the results were “very definitively negative.”
The study evaluated the impact of adding the TIGIT inhibitor tiragolumab to standard of care with atezolizumab plus carboplatin and etoposide chemotherapy on the basis that “TIGIT is a novel inhibitory immune checkpoint molecule present on immune cells in many cancers, including small-cell lung cancer,” Rudin said. Inhibiting TIGIT with tiragolumab “may synergize with other therapies […] to amplify the tumor response,” he explained.
In the primary data analysis set, which excluded patients with a history or presence of brain metastases at baseline, PFS was a median 5.4 months among the 196 patients randomly assigned to receive induction tiragolumab 600 mg plus atezolizumab 1200 mg, carboplatin 5 mg/mL per minute, and etoposide 100 mg/m2 every 3 weeks for four cycles followed by tiragolumab plus atezolizumab maintenance until disease progression, loss of clinical benefit, or unacceptable toxicity.
By comparison, median PFS was 5.6 months in the 201 patients who received placebo plus atezolizumab and chemotherapy, a nonsignificant difference.
Interim median OS in the primary analysis set was 13.6 months in both arms and there were also no significant differences between the two groups in either outcome when patients with brain metastases were included.
In this full analysis set, median PFS was 5.1 months among the 243 patients who received tiragolumab and 5.4 months among the 247 who were given placebo. Median OS was 13.1 and 12.9 months respectively.
The presenter showed that the objective response rate in the full analysis set was ”numerically higher, but not meaningfully so” with tiragolumab versus placebo (70.8 vs 65.6%).
And he noted that there were no new safety signals identified relative to standard of care.
Rudin said that his team will continue to follow-up participants to the planned primary OS analysis and also conduct biomarker analyses on the cohort, but he concluded that “based on [the current] data, targeting TIGIT in extensive-stage small-cell lung cancer does not appear to be therapeutically relevant.”
He added that “investigation of tiragolumab is ongoing in multiple other disease contexts including non-small-cell lung cancer and esophageal cancer.”
Chandra Prakash Belani, from Penn State Cancer Institute in Hershey, Pennsylvania, USA, discussed what might have led to a negative outcome for the trial and suggested it may be because it was based on preclinical rationale which “did not prove to be true and that is unfortunate.”
He added: “I think that we should probably be careful and see whether there is clinical activity [first].”
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