Dr Tripathi on the NEMIO Trial of Durvalumab Plus Chemo With/Without Tremelimumab in MIBC

Abhishek Tripathi, MD, genitourinary medical oncologist, City of Hope, discusses key data from the phase 1/2 NEMIO trial of durvalumab (Imfinzi) with or without tremelimumab (Imjudo) in combination with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) in patients with muscle-invasive bladder cancer (MIBC).

The non-comparative, randomized trial was designed to evaluate the efficacy and safety of combining chemotherapy with an anti-PD(L)-1 in the neoadjuvant setting for patients with localized MIBC treated with radical cystectomy, Tripathi begins.

Patients were required to have clinical stage T2-T4a and N1 or lower disease and be eligible for cisplatin and radical cystectomy therapy, he details. A total of 121 patients were enrolled onto the study and randomly assigned 1:1 to durvalumab plus ddMVAC vs durvalumab, ddMVAC and tremelimumab. The cohorts were not statistically compared with each other, Tripathi notes. All patients were planned for radical cystectomy following systemic, neoadjuvant therapy. The study's co-primary end points were pathologic complete response (pCR) and safety outcomes, he adds.

 showed that the secondary end point of pathologic downstaging (≤ypT1N0) was 71% with the durvalumab doublet vs 61% with the tremelimumab triplet regimen, Tripathi reports, adding that pCRs were also similar between the two cohorts at 49% in the doublet arm, and 47% in the triplet arm. Furthermore, the 1-year disease-free survival rate was 80% (95% CI, 70%-91%) with doublet therapy and 90% (95% CI, 82%-98%) with the triplet therapy regimen at a median follow-up of 15 months (Interquartile range [IQR], 14.3-16.4); the 1-year overall survival rates were 89% (95% CI, 81%-98%) and 97% (95% CI, 92%-100%), respectively, at a median follow-up of 16 months (IQR, 14.9-20.9). A total of 34% of patients had residual muscle-invasive disease.

The safety profile was in line with what has been previously reported with the combination of chemotherapy and immunotherapy, although the triplet therapy regimen was associated with a relatively high incidence of treatment-related adverse effects (TRAEs), Tripathi notes. The most common all-grade TRAEs in both arms were fatigue (71 in the doublet arm; 85% in the triplet arm), nausea (68; 85%), and anemia (57; 63).

Overall, the combination of neoadjuvant ddMVAC plus durvalumab with or without tremelimumab was safe and demonstrated initial efficacy in patients with MIBC.

Videos

Abhishek Tripathi, MD, discusses the phase 1/2 NEMIO trial of durvalumab/chemotherapy with/without tremelimumab in muscle-invasive bladder cancer.

Dr Tripathi on the Use of Frontline Nivolumab/Chemotherapy in Urothelial Carcinoma

Abhishek Tripathi, MD, genitourinary medical oncologist, City of Hope, discusses key data from the phase 3 CheckMate 901 trial (NCT03036098) evaluating concurrent nivolumab (Opdivo) plus chemotherapy in metastatic or unresectable urothelial carcinoma, highlighting its clinical significance in the frontline setting.

The randomized, open-label trial assessed overall survival (OS) and progression-free survival (PFS) outcomes using nivolumab in combination with chemotherapy vs chemotherapy alone in cisplatin-eligible patients with previously untreated, metastatic or unresectable urothelial carcinoma, Tripathi reports. A total of 608 patients were included in the study and were randomly assigned in a 1:1 ratio to receive either nivolumab with gemcitabine/cisplatin followed by nivolumab maintenance therapy or standard gemcitabine/cisplatin alone.

Data from the phase 3 trial were presented at the 

, showing that the nivolumab combination was shown to significantly increase both OS and PFS compared with chemotherapy alone, Tripathi states. The median OS was 18.9 months (95% CI, 14.7-22.4) with chemotherapy alone vs 21.7 months (95% CI, 18.6-26.4) in the combination group (HR, 0.78; 95% CI, 0.63-0.96; 

 = .0171), he details. Additionally, the median PFS was 7.9 months (95% CI, 6.1-7.8) with the nivolumab combination compared with 7.6 months (95% CI, 6.1-7.8 with chemotherapy alone (HR, 0.72; 95% CI, 0.59-0.88; 

This trial represents one of the first studies to demonstrate a survival benefit with the combination of cisplatin-based chemotherapy and immunotherapy in the frontline setting for cisplatin-eligible patients with urothelial carcinoma, Tripathi emphasizes. However, the study faces challenges in the context of other combination studies reporting similar outcomes, he notes. It will be important to compare the regimen's utilization to other novel, highly-effective combination therapies, such as enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda), Tripathi explains. However, in settings where access to novel agents is challenging or cost-effectiveness is crucial, the cisplatin-gemcitabine and nivolumab combination offers a reasonable treatment option for patients with metastatic disease, he concludes.

Abhishek Tripathi, MD, discusses the significance of data from the phase 3 CheckMate 901 trial in metastatic or unresectable urothelial carcinoma.

Abhishek Tripathi, MD

Articles

Dr Tripathi on the NEMIO Trial of Durvalumab Plus Chemo With/Without Tremelimumab in MIBC

Dr Tripathi on the Use of Frontline Nivolumab/Chemotherapy in Urothelial Carcinoma