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Tecentriq-Tiragolumab-Chemo Combo Showed Improved Survival in ESCC

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In patients with esophageal squamous cell carcinoma, the combination of Tecentriq, tiragolumab and chemotherapy improved survival outcomes, research found.

conceptual image of an esophagus

Adding Tecentriq and tiragolumab to chemotherapy improved outcomes in patients with a certain type of esophageal cancer.

Patients with esophageal squamous cell carcinoma (ESCC) demonstrated better survival outcomes after receiving Tecentriq (atezolizumab) plus tiragolumab and chemotherapy as frontline therapy, compared with chemotherapy alone, according to a phase 3 trial.

Findings from the phase 3 SKYSCRAPER-08 trial were presented at the 2024 Gastrointestinal Cancers Symposium.

Tiragolumab is a type of monoclonal antibody directed against TGIT, a coinhibitory receptor and immune checkpoint that is expressed on activated T cells that are in multiple cancer types, including esophageal carcinoma.

Tecentriq is a drug that binds onto the protein PD-L1 to help immune cells destroy cancer cells more efficiently, according to the National Cancer Institute. This drug is also a monoclonal antibody and immune checkpoint inhibitor.

The results from the study showed that the combination of Tecentriq plus tiragolumab and chemotherapy improved overall survival (OS; time from diagnosis to end of treatment when a patient is still alive) and progression-free survival (PFS; time during and after treatment when a patient lives with the disease but it does not worsen) in patients with ESCC.

There were 448 patients who were randomly assigned evenly in two arms to receive either tiragolumab, Tecentriq, cisplatin and paclitaxel — the latter of the two are types of chemotherapy— or a placebo with cisplatin and paclitaxel. In the Tecentriq plus tiragolumab and chemotherapy arm, there were 226 patients and there were 222 patients in the placebo-containing arm.

Treatment in both arms continued until benefits were not improving or unacceptable toxicity.

The median age in the Tecentriq plus tiragolumab and chemotherapy arm was 63 years versus 63 years in the placebo arm. Most patients in both arms were less than 65 years of age, identified as male (87.3% versus 88.8%), did not receive previous curative treatment (64.2% versus 63.8%), had one or fewer organs with metastases (53.7% versus 52.6%) and had an ECOG performance status of 1 (75.1% versus 74.1%), meaning they could independently perform everyday tasks.

All patients in both arms identified as Asian. Further, 23.1% of patients in the Tecentriq plus tiragolumab and chemotherapy arm had metastatic liver disease versus 20.3% in the placebo arm.

“Recently, the combination of anti-PD-1 immunotherapy plus chemotherapy has emerged as a new first-line standard therapy (for patients with ESCC), yet treatments with higher efficacy are still needed,” Dr. Chih-Hung Hsu of the National Taiwan University Hospital, said during the presentation. “In previous studies, tiragolumab when combined with other immunotherapies, such as (the) anti-PD-L1 (therapy Tecentriq), has been shown to augment anti-tumor responses.”

The primary endpoints (main results measured after the end of study to see if treatment worked) were OS and PFS. Secondary endpoints included objective response rate (ORR; percentage of patients who showed a partial or complete response to treatment) and duration of response (DoR; time from the start of treatment until disease progression or death in patients who had a partial or complete response), as well as safety.

At the Feb. 13, 2023 data cutoff, results from the final OS analysis of the trial demonstrated that the 226 patients who received tiragolumab plus Tecentriq and chemotherapy achieved a median OS of 15.7 months, compared with 11.1 months among the 222 patients who received placebo plus chemotherapy. The 12-month OS rates were 60.6% versus 46.1%, respectively, and the 18-month OS rates were 47.2% versus 33.8%.

Regarding PFS at the June 15, 2022 data cutoff, patients in the tiragolumab plus Tecentriq arm experienced a median PFS of 6.2 months, compared with 5.4 months in the placebo arm. The 12-month PFS rates were 24.0% versus 6.1%, respectively.

The secondary endpoints from the study established that the ORR among patients in the tiragolumab plus Tecentriq arm was 59.7% with a complete response (CR; disappearance of cancer) rate of 11.5%. In the placebo arm, the ORR was 45.5% including a CR rate of 3.2%.

The median DOR was 7.1 months compared with 4.3 months, in the tiragolumab plus Tecentriq and placebo arms, respectively. At the data cutoff, 47.4% and 23.8% of patients had an ongoing response. Approximately 19% of patients in the tiragolumab plus Tecentriq arm, achieved stable disease compared with 26.1% in the placebo arm; progressive disease rates were 9.3% versus 19.8%.

In terms of safety, any-grade side effects occurred at rates of 98.7% versus 99.6% in the tiragolumab plus Tecentriq and placebo arms, respectively, with 98.2% being treatment-related in both arms.

Patients in the tiragolumab plus Tecentriq and placebo arms experienced grade 3 to 4 side effects (68.0% versus 61.2%, respectively), meaning their side effects were serious to life-threatening. Deaths caused by side effects occurred in 5.7% versus 4.8%, serious side effects occurred in 41.2% versus 39.2%), side effects leading to treatment discontinuation occurred in 19.7% versus 10.6%) and side effects leading to dose modification or interruption occurred in 64.0% versus 56.4%).

Treatment-related deaths in the tiragolumab plus Tecentriq arm were immune-mediated lung disease, pneumonitis, cardiac arrest, gastrointestinal hemorrhage, liver failure and bacterial pneumonia. In the placebo arm, two treatment-related deaths were caused by gastrointestinal infection.

At the data cutoff, 32 patients were still undergoing treatment in the tiragolumab plus Tecentriq arm and 196 discontinued due to disease progression, 28 because of withdrawal, 27 because of side effects, 14 because of death, 12 because of physician decision, one because of symptomatic deterioration, one because of protocol deviation and one being lost to follow-up.

In the placebo arm, 10 patients were ongoing on treatment, and 217 discontinued due to disease progression in 149 patients, 25 because of withdrawal, 11 because of side effects, 11 because of death, 17 because of physician decision, three because of symptomatic deterioration and one because of protocol deviation.

“The overall safety profile of this combination has been consistent with previous observations and there were no new safety signals,” Hsu said. “These data support that this combination may represent an alternative first-line treatment option for patients with unresectable, locally advanced and metastatic ESCC.”

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