Background
AtTEnd (ENGOT-en7/MaNGO) was a phase III double-blind, placebo-controlled trial (n=551) evaluating the addition of atezolizumab (anti-PD-L1) to standard carboplatin-paclitaxel chemotherapy as first-line treatment for advanced or recurrent endometrial carcinoma or carcinosarcoma. It tested PD-L1 inhibition as a complementary approach to PD-1 inhibition (pembrolizumab, dostarlimab) in the same indication, with prospective MMR stratification.
Interventions and follow up
Arm A (placebo): Carboplatin AUC 5–6 + paclitaxel 175 mg/m² q21d ×6–8 cycles + placebo q3w → placebo maintenance until progression
Arm B (atezolizumab): Carboplatin AUC 5–6 + paclitaxel 175 mg/m² q21d ×6–8 cycles + atezolizumab 1200 mg q3w → atezolizumab maintenance until progression
Primary endpoints: PFS (dMMR and overall populations) and OS (overall, hierarchically tested)
Median follow-up: 28.3 months
Arm B (atezolizumab): Carboplatin AUC 5–6 + paclitaxel 175 mg/m² q21d ×6–8 cycles + atezolizumab 1200 mg q3w → atezolizumab maintenance until progression
Primary endpoints: PFS (dMMR and overall populations) and OS (overall, hierarchically tested)
Median follow-up: 28.3 months
Results
dMMR mPFS (n=81 atezo, n=44 placebo): NE vs 6.9 months; HR 0.36, 95% CI 0.23–0.57, P=.0005
Overall mPFS (n=360 atezo, n=188 placebo): 10.1 vs 8.9 months; HR 0.74, 95% CI 0.61–0.91, P=.022
Interim mOS (overall): 38.7 vs 30.2 months; HR 0.82, 95% CI 0.63–1.07, P=.048 (did not cross pre-specified stopping boundary; trial ongoing)
Overall mPFS (n=360 atezo, n=188 placebo): 10.1 vs 8.9 months; HR 0.74, 95% CI 0.61–0.91, P=.022
Interim mOS (overall): 38.7 vs 30.2 months; HR 0.82, 95% CI 0.63–1.07, P=.048 (did not cross pre-specified stopping boundary; trial ongoing)
Adverse events
Hematologic: Neutropenia 27% (atezo) vs 28% (placebo); anemia 14% vs 13%
Other: Treatment-related serious AEs 13% vs 3%; treatment-related deaths 2 (one pneumonia per arm); immune-mediated AEs higher with atezolizumab
Other: Treatment-related serious AEs 13% vs 3%; treatment-related deaths 2 (one pneumonia per arm); immune-mediated AEs higher with atezolizumab
Conclusions
Atezolizumab plus carboplatin-paclitaxel significantly improved PFS in dMMR endometrial cancer and in the overall population, with a particularly striking benefit in dMMR tumors, confirming the importance of MMR biomarker selection for first-line IO-chemotherapy combinations in endometrial cancer.
Key Limitations
2:1 randomization (not 1:1) limits comparator-arm power; the dMMR subgroup is small (~23% of enrolled); OS did not cross the interim stopping boundary — final OS data pending; results are broadly consistent with but not superior to concurrent pembrolizumab and dostarlimab trials; atezolizumab (PD-L1) vs PD-1 comparisons are indirect.
Clinical Context
AtTEnd joins NRG-GY018 (pembrolizumab) and RUBY (dostarlimab) as positive phase III trials of IO plus carbo/pac in first-line endometrial cancer. Collectively these have made IO-containing chemotherapy the standard of care for first-line advanced endometrial cancer. Atezolizumab is not FDA-approved in endometrial cancer (pembrolizumab and dostarlimab hold the approvals), but AtTEnd confirms the class effect. The dMMR benefit (HR 0.36) is consistent across trials; the overall benefit (HR 0.74) is most modest in AtTEnd. ESMO guidance recognizes IO-chemotherapy combinations in this setting.