麻豆传媒

CHICAGO -- Combining the novel human anti-TIGIT monoclonal antibody tiragolumab with atezolizumab (Tecentriq) plus chemotherapy failed to improve outcomes in patients with untreated extensive-stage small cell lung cancer (SCLC), according the phase III trial presented here.

In the primary analysis, patients who never had brain metastases and were treated with the tiragolumab-based combination had a median progression-free survival (PFS) of 5.4 months compared with 5.6 months in patients who received placebo plus atezolizumab/chemotherapy (HR 1.11, 95% CI 0.89-1.38).

Overall survival (OS) was an identical 13.6 months in both groups, reported Charles M. Rudin, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City, at the annual meeting of the American Society of Clinical Oncology (ASCO).

The results were similar when patients with brain metastases were included, with a PFS of 5.1 months with tiragolumab versus 5.4 months with placebo (HR 1.08, 95% 0.89-1.31), and OS of 13.1 months and 12.9 months, respectively (HR 1.02, 95% 0.80-1.30).

And, "there doesn't appear to be any subgroup that selectively benefits from the addition of tiragolumab here," Rudin said when presenting the findings at a late-breaking clinical trial session.

"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," Rudin said. "I will point out, however, that the investigation of tiragolumab is ongoing in multiple other disease contexts, including non-small cell lung cancer and esophageal cancer."

Regarding safety, there was little difference in side effect signals between the arms, Rudin reported, with grade 3 0r 4 adverse events of special interest occurring in 53.6% of patients in the tiragolumab arm and 48.0% in the placebo arm.

Rudin concluded that the PFS and OS results in both arms of the trial "help to support the prior results observed in ," which found atezolizumab plus carboplatin and etoposide chemotherapy better than chemotherapy alone. The new results further confirm the potential benefit of that triplet combination "as a standard of care for the treatment of newly-diagnosed extensive-stage small cell lung cancer."

He added that patients in the trial are still being followed and biomarker analyses are ongoing.

Biomarker Challenges

However, ASCO discussant Chandra Prakash Belani, MD, of Penn State Cancer Institute in Hershey, Pennsylvania, said that studying biomarkers in SCLC "is a big challenge."

"Small cell lung cancers are usually not resected," he pointed out, adding that diagnostic biopsy samples may be inadequate or necrotic and that insufficient quality and/or quantity of tumor material can make it difficult to study the expression of PD-L1 and other biomarkers.

"Honestly, I don't think any biomarker is going to pull out a group that benefits from tiragolumab," Rudin said. "We are very interested in biomarkers for defining the subgroups ... who benefit from immunotherapy in this disease. And I think this large data set, where biospecimen collection was actually quite good, should serve as a nice template in which to begin to analyze that. In addition to the other phase III trials that have been completed in this space, I think we now have a good substrate for looking at this question."

Study Details

In explaining the rationale behind SKYSCRAPER-02, Rudin noted that while the benefit shown by IMpower133 when adding atezolizumab to a backbone of carboplatin and etoposide "was clearly a clinical advance, the vast majority of patients with extensive-stage small cell lung cancer continue to suffer disease progression, with a median of about five and a half months from the time of diagnosis."

"So there is clearly a major unmet need for the treatment of these patients," Rudin said. He and his colleagues hypothesized tiragolumab may synergize with other immunotherapies to amplify an anti-tumor response.

Patients in the trial were under age 65 (median age 48 in the tiragolumab arm and 47 in the placebo arm). Most were previous or current smokers, and about one-quarter were of Asian descent. Good performance status was required, and brain metastases were present in about 19% of patients, with most of those untreated at the time those patients started systemic therapy.

The investigators randomized patients 1:1 to receive induction with tiragolumab 600 mg intravenously or placebo, combined with the triplet of atezolizumab plus carboplatin and etoposide for four 21-day cycles, followed by maintenance tiragolumab or placebo combined with atezolizumab every 3 weeks until disease progression or loss of clinical benefit.

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