Drug Update · Oncology

FDA Approves Durvalumab for BCG‑Naive High‑Risk NMIBC: DFS HR 0.68 in POTOMAC

September 10, 2026

FDA approval date

05/28/2026

DFS hazard ratio

0.68 (95% CI: 0.50-0.93)

Recommended dose (≥ 30 kg)

1,500 mg IV every 4 weeks for 13 cycles

Trial

POTOMAC (NCT03528694), randomized, open‑label, multicenter

Randomized patients

1,018

Clinical Perspective

This FDA action affects oncologists, urologists, and advanced practice providers caring for adults with BCG‑naïve, high‑risk NMIBC by adding an FDA‑approved systemic PD‑L1 agent to use in combination with BCG induction and maintenance ^[2]^[1]. The POTOMAC data support use of durvalumab plus BCG induction and maintenance to improve disease‑free survival compared with BCG induction and maintenance alone in the trial population ^[2]. Important open questions include how to apply these results to individual patients with differing high‑risk features or comorbidities, and which biomarkers, if any, predict the greatest benefit in routine practice?

Dr. Rahul Verma, MBBS, MD (General Medicine), DM (Medical Oncology) · Oncology

Durvalumab (Imfinzi) was approved by the FDA on May 28, 2026, in combination with Bacillus Calmette‑Guérin (BCG) for the treatment of adult patients with BCG‑naïve, high‑risk non‑muscle‑invasive bladder cancer (NMIBC) ^[2]. Approval was supported by the randomized POTOMAC trial, which showed a disease‑free survival (DFS) benefit for durvalumab plus BCG versus BCG induction and maintenance alone (hazard ratio 0.68; 95% CI: 0.50, 0.93) ^[2]^[3].

Clinical Context

Durvalumab is a programmed death‑ligand 1 (PD‑L1) blocking antibody marketed as Imfinzi by AstraZeneca and is an anti‑PD‑L1 immunotherapy described in the prescribing information ^[1]. The FDA label now includes an indication for use of durvalumab in combination with BCG for adult patients with BCG‑naïve, high‑risk NMIBC ^[1]^[2]. In the POTOMAC program the FDA used disease‑free survival (DFS) as the primary efficacy measure; the FDA noted the trial’s randomized, open‑label, multicenter design in its approval summary and referenced the trial’s investigator‑assessed DFS outcome when announcing the approval ^[2]^[3]. The prescribing information specifies patient selection and dose and administration details for the new NMIBC indication ^[1].

Key Findings

The POTOMAC trial showed durvalumab plus BCG induction and maintenance reduced the risk of disease recurrence, progression to muscle‑invasive disease, metastatic disease, or death by 32% versus BCG induction and maintenance alone (HR 0.68; 95% CI: 0.50-0.93), with a two‑sided p‑value of 0.0154; median DFS was not reached for either arm in the analysis reported by the FDA ^[2].
POTOMAC was a randomized, open‑label, multicenter trial that enrolled patients with high‑risk NMIBC after transurethral resection of bladder tumor; high‑risk NMIBC was defined in the FDA summary as T1 tumor, Grade 3/high‑grade tumor, carcinoma in situ (CIS), or multiple, recurrent, and large tumors ^[2]^[3].
The trial randomized 1,018 patients (1:1:1) to durvalumab plus BCG induction and maintenance, durvalumab plus BCG induction, or BCG induction and maintenance; the comparison for the approved indication was durvalumab plus BCG induction and maintenance versus BCG induction and maintenance alone ^[3]^[2].

Safety & Tolerability

The prescribing information lists immune‑mediated adverse reactions and infusion‑related reactions as warnings and precautions for durvalumab, and includes specific monitoring recommendations and guidance to withhold or discontinue based on severity ^[1].
For patients with BCG‑naïve high‑risk NMIBC, the prescribing information identifies the most common adverse reactions (≥ 20%) observed in clinical trials: increased glucose, increased AST, increased lipase, increased ALT, increased GGT, urinary tract infection, increased potassium, dysuria, decreased hemoglobin, hematuria, increased serum creatinine, musculoskeletal pain, decreased lymphocytes, urinary frequency, decreased sodium, fatigue, rash, and pyrexia ^[1].

Study Design

POTOMAC (ClinicalTrials.gov NCT03528694) was a randomized, open‑label, multicenter Phase 3 trial that enrolled 1,018 patients with high‑risk NMIBC after transurethral resection of bladder tumor and randomized them 1:1:1 to receive durvalumab plus BCG induction and maintenance, durvalumab plus BCG induction, or BCG induction and maintenance alone ^[3]^[2]. The major efficacy outcome measure for the approved comparison was investigator‑assessed DFS, defined as time from randomization to first recurrence of high‑risk NMIBC, persistent CIS, muscle‑invasive bladder cancer, metastatic disease, or death ^[2]^[3]. Median follow‑up and the number of DFS events were reported in the trial publications and FDA summary ^[3]^[2].

FAQ

Q1 What is durvalumab (Imfinzi) approved for?

Durvalumab (Imfinzi) is approved by the FDA in combination with Bacillus Calmette‑Guérin (BCG) for the treatment of adult patients with BCG‑naïve, high‑risk non‑muscle‑invasive bladder cancer (NMIBC). The approval was announced by the FDA on May 28, 2026, and references the POTOMAC randomized trial as the basis for the indication. The label and full prescribing information include patient selection and dosing guidance.

Q2 How does durvalumab work?

Durvalumab is a programmed death‑ligand 1 (PD‑L1) blocking antibody that binds PD‑L1 and blocks its interaction with PD‑1 and CD80, releasing inhibition of immune responses; this mechanism is described in the prescribing information for Imfinzi. The label frames durvalumab as an anti‑PD‑L1 immunotherapy used in multiple tumor types and now in combination with BCG for BCG‑naïve high‑risk NMIBC.

Q3 What is the recommended dose of durvalumab for this indication?

The recommended durvalumab dose for patients with body weight ≥ 30 kg is 1,500 mg administered intravenously every 4 weeks for 13 cycles in combination with BCG induction and maintenance. Treatment should continue until recurrence of high‑risk disease, disease progression, unacceptable toxicity, or a maximum of 13 cycles, per the FDA approval and prescribing information. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects?

The prescribing information lists immune‑mediated adverse reactions and infusion‑related reactions as key warnings and precautions. In patients with BCG‑naïve high‑risk NMIBC treated in clinical trials, the most common adverse reactions (≥ 20%) included increased glucose, increased AST, increased lipase, increased ALT, increased GGT, urinary tract infection, increased potassium, dysuria, decreased hemoglobin, hematuria, increased serum creatinine, musculoskeletal pain, decreased lymphocytes, urinary frequency, decreased sodium, fatigue, rash, and pyrexia. The label also notes monitoring guidance and management recommendations for immune‑mediated events.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Durvalumab for BCG‑Naive High‑Risk NMIBC: DFS HR 0.68 in POTOMAC

Direct Clinical Takeaway & Evidence Summary

FDA Approves Durvalumab for BCG‑Naive High‑Risk NMIBC: DFS HR 0.68 in POTOMAC

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Cite & Reference This Monograph

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