Tiragolumab/Atezolizumab Has “No Path Forward” in Cervical Cancer

The drug combination of tiragolumab with atezolizumab (Tecentriq), studied in the phase 2 SKYSCRAPER-04 trial (NCT04300647), was found to have no historical statistical significance, which has prompted investigators to determine the combination has no future in treating patients with PD-L1–positive recurrent cervical cancer, according to Ritu Salani, MD.

In a conversation with CancerNetwork®, Salani, the Gynecologic Oncology Fellowship Director at the University of California Los Angeles Health, and the Gynecologic editorial board member for the journal ONCOLOGY®, discussed the safety findings of the study. Despite the combination of TIGIT and PD-L1 or PD-1 inhibitors being safe for patients, Salani says there is no future for that combination alone for patients with cervical cancer. This treatment combination is currently being used for other disease sites, with similar safety findings.

According to data from the study, the treatment showed numerical improvement in overall response rate (ORR) in patients with PD-L1–positive recurrent cervical cancer but did not reach statistical significance compared with a historical reference. Across the total patient population, the ORR was 19.0% in patients who received tiragolumab plus atezolizumab compared with 15.6% in those who were treated with atezolizumab alone.

In terms of safety, adverse effects (AEs) occurred in 94% and 91% of patients in the combination and monotherapy arms, respectively. Grade 3 or 4 AEs occurred in 44% and 31% of patients, respectively. AEs that led to discontinuation occurred in 3% and 4% of patients, respectively.

Future studies combining the tiragolumab/atezolizumab combination with other agents, such as bevacizumab (Avastin), could be possible.

Transcript:

One important message is that the checkpoint inhibitor therapy was safely administered. There were no new safety signals. This has been used across other disease sites [as well]. This [study] just continues to add to that experience. Even with the addition of the TIGIT inhibitor, [there was a] minimal increase in adverse effects [AEs]. They were slightly higher, but no grade 5 AEs and very few grade 3 or 4 AEs [were observed]. It is a safe combination; it just wasn’t as effective as we were hoping.

In this patient population, the addition of a TIGIT and a PD-L1 or PD-1 inhibitor probably does not have any path forward in that combination alone. [In future studies, clinicians should] consider adding it to bevacizumab or other agents that might have some viability, but this is probably the end of a TIGIT PD-1/PD-L1 combination.

Reference

Salani R, Monk BJ, Kim Y, et al. Efficacy and safety results from SKYSCRAPER-04: An open-label randomized phase 2 trial of tiragolumab plus atezolizumab for PD-L1-positive recurrent cervical cancer. Presented at 2023 Annual Global Meeting of the International Gynecologic Cancer Society; November 5-7, 2023; Seoul, Korea; abstract PO002/156.