Regulatory Decision Summary for Imfinzi (durvalumab)

The purpose of this supplemental new drug submission was to seek market authorization for Imfinzi (durvalumab), in combination with platinum-based chemotherapy, followed by maintenance with Imfinzi as monotherapy or in combination with olaparib, for the first-line treatment of patients with advanced or recurrent endometrial cancer (EC).

After evaluation of the submitted data package, Health Canada authorized Imfinzi for the following indication:

Imfinzi in combination with carboplatin and paclitaxel is indicated for the first-line treatment of adult patients with primary advanced or recurrent mismatch repair deficient (dMMR) EC who are candidates for systemic therapy, followed by maintenance treatment with Imfinzi as monotherapy.

Authorization was based on the results from an international, multi-centre, randomized, placebo-controlled trial. In this trial, patients (n = 718) with advanced or recurrent EC who were candidates for systemic therapy were randomized in 1:1:1 to receive Imfinzi in combination with carboplatin and paclitaxel (standard of care + durvalumab [SOC + D]; n = 238), carboplatin and paclitaxel (SOC; n = 241) or an additional investigational arm (n = 239). MMR status was a stratification factor (dMMR versus MMR proficient).

The primary efficacy endpoint was progression-free survival (PFS) as determined by investigator assessment using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria. Overall survival (OS) was a key secondary endpoint. The statistically significant improvement in PFS with SOC + D versus SOC in the overall population was primarily attributed to patients with dMMR tumors, based on a pre-specified exploratory subgroup analysis by the MMR status. Among 95 patients with dMMR tumors, the median PFS was not reached in the SOC + D arm and 7.0 months in the SOC arm (hazard ratio: 0.42; 95% confidence interval [CI]: 0.22, 0.80); the median OS was not reached in the SOC + D arm and 23.7 months in the SOC arm, although the OS data were immature and 26% of patients died in this subpopulation at the time of the PFS analysis.

The adverse events reported in at least 30% of patients who were treated with Imfinzi in combination with carboplatin and paclitaxel were alopecia, anemia, nausea, fatigue, diarrhea and arthralgia. The safety finding of Imfinzi was consistent with the previous observations. The risks associated with the uses of Imfinzi in combination with carboplatin and paclitaxel are adequately captured in the Product Monograph (PM).

In view of the PFS improvement observed with Imfinzi in combination with carboplatin and paclitaxel, and the manageable safety profile, the benefits outweigh the risks for patients with dMMR advanced or recurrent EC.

The recommended dose of Imfinzi is 1,120 mg in combination with carboplatin and paclitaxel for 6 cycles, followed by maintenance with Imfinzi 1,500 mg every 4 weeks as monotherapy until disease progression or unacceptable toxicity. View the PM for details.

For further details about Imfinzi, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.