Emma Hudson

Phase III double-blind randomized placebo controlled trial of atezolizumab in combination with carboplatin and paclitaxel in women with advanced/recurrent endometrial carcinoma: the Asian cohort of the AtTEnd/ENGOT-EN7 trial

This post-hoc analysis of the AtTEnd trial explored differences in the prognostic characteristics and in the efficacy of atezolizumab between Asians and non-Asians. The role of Asian race was evaluated on progression-free survival (PFS) using Cox-models and on time to appearance of new lesions using Fine and Gray models. From October 2018 to February 2022, 549 patients were randomized, of whom, 20.4% were Asian. Asians showed a better prognostic profile in terms of age, body mass index, Eastern Cooperative Oncology Group performance status, disease status and previous treatments. The prognostic impact of Asian race on PFS was confirmed in the placebo arm (adjusted hazard ratio [HR]=0.41; 95% confidence interval [CI]=0.24-0.70). In proficient mismatch repair (pMMR) tumors, the HRs for PFS comparing atezolizumab versus placebo were 0.82 (95% CI=0.63-1.05) in non-Asians, and 1.42 (95% CI=0.80-2.50) in Asians. In the pMMR population randomized to atezolizumab, the subdistribution HRs comparing Asians to non-Asians were 0.68 (95% CI=0.43-1.09) for progression with new lesions and 1.21 (95% CI=0.73-2.03) for progression without new lesions. Asians showed a higher occurrence of severe adverse events in atezolizumab compared to placebo arm (Asians: 82.1% vs. 64.3%, p=0.036; non-Asian: 63.3% vs. 63.6%, p=0.949). Race seems to affect the safety of the addition of atezolizumab and, in pMMR tumors, also its efficacy. In the atezolizumab arm, Asian patients seem to have a lower cumulative incidence of new lesions when primary tumor regrowth was considered a competing risk, and a higher cumulative incidence of primary tumor regrowth when new lesions appearance was the competing risk. ClinicalTrials.gov Identifier: NCT03603184.

Real World Multi-centre UK Review of Nivolumab Monotherapy in Metastatic Endometrial Cancer With Mismatch Repair Deficiency During COVID-19

Immunotherapy checkpoint inhibition has shown improvement in efficacy and survival in patients with mismatch repair deficient (MMRd) advanced endometrial cancer (mEC) compared to chemotherapy. This is combined with chemotherapy in the first-line setting or as monotherapy in later lines of therapy. To assess the efficacy, survival and toxicity of nivolumab monotherapy in metastatic endometrial cancer (mEC) in both first and later lines of therapy as used in the NICE COVID-19 systemic anti-cancer (SACT) guidelines. A multi-centre retrospective review of mEC patients with associated MMRd who received nivolumab as per NICE COVID NG161 at 10 NHS cancer centres. Patient demographics, molecular classification and previous treatments were recorded in addition to treatment responses, duration of response, overall survival, progression-free survival and toxicities. Kaplan-Meier curves analyse the survival data. 52 patients were identified. Median age was 67 (37-81) years. 87.5% of patients had endometrioid histology and 75% were oestrogen receptor (ER) positive. 10.4% patients were p53 mutated. 33.3% of mEC patients were stage IV at diagnosis. 30 (62.5%) patients received nivolumab as first-line mEC therapy. 33 (68.8%) patients received nivolumab 4-weekly. Treatment response was clinician-observed in 34 (70.8%) patients, with 7 (14.5%) more having stable disease. 52%, 45% and 36% of patients were progression-free at 12, 18 and 24months, respectively. 75%, 55% and 47% of patients were alive at 12, 18 and 24 months. There was no significant difference between survival or response whether nivolumab was given in the first line or subsequent lines. 29 (60.4%) patients have discontinued treatment with 23 (44.2%) being due to progressive disease or death. 18 (37.5%) patients developed G1-2 toxicity, and 3 (6.25%) patients discontinued due to G3 toxicity. This retrospective cohort shows that nivolumab monotherapy has good real-world disease control of mEC patients with MMR deficiency. Toxicity rates were low, and checkpoint monotherapy may be a viable option for selected first-line MMRd mEC patients.

Atezolizumab Trial in Endometrial Cancer - AtTEnd

Atezolizumab is an engineered humanised monoclonal immunoglobulin G1 antibody that binds selectively to PD-L1 and prevents its interaction with PD-1 and B7-1. In May 2016 atezolizumab was approved by the FDA for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant); in October 2016 it was approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumor has EGFR or ALK gene abnormalities. Finally, in April 2017 atezolizumab was granted accelerated approval by FDA for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy. Combinations of atezolizumab with chemotherapeutic agents and/or targeted therapies were studied in different solid tumors such as melanoma, NSCLC, renal cell carcinoma and colorectal carcinoma. From these studies the AE profile of atezolizumab combinations were consistent with that of the individual agents. Finally, preliminary results of a Phase Ia study of Atezolizumab (NCT01375842) monotherapy in relapsed endometrial cancer were reported as abstract at ASCO 2017. Fifteen patients were evaluated for safety and efficacy with a minimum follow-up of 11.2 months. No G4-5 related AEs occurred. Regarding efficacy ORR was 13% \[2/15\] by RECIST. Atezolizumab seemed to have a favorable safety profile, with durable clinical benefit in some patients. Further studies with atezolizumab are warranted given its promising results in advanced endometrial cancer and the limited efficacy of current treatment options.