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.

Results presented at the 2023 ESMO Congress 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.