Chemo Plus Tecentriq Shows Improvements in Endometrial Carcinoma

A phase 3 trial demonstrated progression-free survival improvements with Tecentriq-chemotherapy combination in patients with endometrial carcinoma.

The treatment combination of Tecentriq (atezolizumab) and platinum-based chemotherapy demonstrated benefits for patients with frontline advanced or recurrent endometrial carcinoma, specifically patients with deficient mismatch repair (dMMR) status, according to data from a phase 3 trial presented at the ESMO Congress 2023.

As defined by National Cancer Institute, dMMR describes cells that mutate and could lead to cancer, which is common among patients with endometrial cancer.

The randomized, placebo-controlled phase 3 AtTEnd trial included 551 patients, in which 360 patients received Tecentriq with two chemotherapy drugs, Paraplatin (carboplatin) and paclitaxel until disease progression. Of the 551 total patients, 189 patients received a placebo with Paraplatin and paclitaxel until disease progression.

The presenter, Nicoletta Colombo, director of gynecological cancer medical treatments, European Institute of Oncology, Milan, Italy, noted that 66 patients were still on maintenance with Tecentriq and 27 with placebo.

“AtTEnd confirms the outstanding efficacy of immune checkpoint inhibitors, including PD-L1 inhibitors, in combination with chemotherapy in patients with advanced/recurrent endometrial carcinoma, particularly in those with dMMR,” Colombo said during the presentation of the data.

Primary Analysis

After a median follow-up of 26.2 months, among the dMMR population, the median progression-free survival (PFS; period during and after treatment when a patient’s disease does not worsen) in the Tecentriq group was not evaluable (meaning that in this cohort, more than half of the patients’ disease had not progressed by the time of follow-up), compared with 6.9 months in the placebo group.

According to the data, the 12-month PFS rates in the Tecentriq and placebo groups were 62.7% and 23.3%, respectively, while 24-month rates were 50.4% and 16%. The risk for disease progression was reduced by 64% with Tecentriq.

Superiority with Tecentriq was confirmed in the all-comer population (median follow-up, 28.3 months), with a median PFS of 10.1 months, compared with 8.9 months with placebo.

The 12-month PFS rates were 44.9% versus 28.8%, respectively, while the 24-month PFS rates were 28.1% versus 17%. The risk for disease progression was reduced by 26% with Tecentriq.

“The PFS improvement in all comers is mainly due to the large effect observed in the dMMR group in which a clear benefit is also seen,” Colombo said.

The investigators also conducted an interim overall survival (OS; period of time from diagnosis or start of treatment when a patient is still alive) analysis, with 43% data maturity; 236 deaths occurred.

Among the all-comer population, the median OS was 38.7 months with Tecentriq, versus 30.2 months with placebo.

Twelve-month OS rates were 80.1%, compared with 74.9%, with Tecentriq and placebo, respectively, while 24-month OS rates were 62.2% versus 58.0%. Treatment with Tecentriq reduced the risk of death by 18%.

In total, 9% of the Tecentriq arm and 24.3% of patients in this analysis of the all-comer population went on to recieve subsequent immunotherapy.

Secondary Analysis

In the dMMR population, the median OS was not evaluable with Tecentriq (meaning more than half of these patients were still alive), compared with 25.7 months with placebo. The 12-month OS rates in the Tecentriq and placebo groups were 86.8% and 66.8%, respectively, while the 24-month OS rates were 75% and 54.2%. Treatment with Tecentriq reduced the risk of death by 59%.

In total, 6.2% of the atezolizumab arm and 40.9% of the placebo arm in the dMMR population went on to subsequent IO.

Among patients in the proficient MMR (pMMR; cells are in a “normal” state and the mismatch repair pathway is functional) population, the median PFS was 9.5 months in the Tecentriq arm, compared with 9.2 months in the placebo arm.

The 12- and 24-month PFS rates in the Tecentriq arm were 39.5% and 21.3%, respectively, compared with 30.2% and 16.4% in the placebo arm). The median OS was 31.5 months with Tecentriq, compared with 28.6 months with placebo. In addition, the 12- and 24-month OS rates with Tecentriq were 77.8% and 57.4%, respectively, versus 77.3% and 58.3% with placebo.

According to Colombo, based on these data, they could not find any PFS or OS benefit in the pMMR population. In total, of the pMMR population, 9.8% and 19.1% of the Tecentriq and placebo groups, respectively, went on to receive subsequent immunotherapy.

However, when evaluating the overall response rate (ORR; percentage of patients who received a partial or complete response to treatment) and duration of response (DOR; length of time when a tumor responds to treatment without growing or spreading), Colombo noted that they “were markedly improved in the dMMR population.”

In the dMMR population, ORR was 82.4% in the Tecentriq group, including 31 complete responses (CRs) and 43 partial responses (PRs), compared with 75.7%, including seven CRs (18.9%) and 21 PRs (56.8%) in the placebo group. Median DOR with Tecentriq, versus placebo, was not evaluable (meaning more than half of these patients’ tumors had not grown or spread) and 4.9 months, respectively.

In the pMMR population, ORR was 75% with Tecentriq, including 27 CRs (13.2%) and 126 PRs (61.8%), compared with 74.6%, including 12 CRs (10.5%) and 73 PRs (64%) with placebo. The median DOR was 7.8 months with Tecentriq versus 7 months with placebo.

“In the pMMR population, there was no benefit in the overall response rate and in the duration of response,” Colombo noted.

In total, 75.6% of side effects were related to Tecentriq, versus 63.8% with placebo, while 25.8% and 14.1%, respectively, of the arms were related to mild to severe side effects. One death occurred in each arm because of treatment.

“The safety profile of the combination of chemotherapy and (Tecentriq) is manageable and consistent with expected toxicities,” Colombo noted.

In the Tecentriq and placebo arms, 290 and 158 patients, respectively, discontinued treatment due to progressive disease (191 versus 131), side effects (65 versus 9), deterioration of clinical condition or clinical decision (15 versus 7), patient refusal (8 versus 3), consent withdrawal (5 versus 4), death (3 versus 2) or another reason (3 versus 2).

“The trial will continue as planned to assess OS,” Colombo concluded.

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