FDA Grants Durvalumab Priority Review for Fixed-Dose Use in NSCLC and Bladder Cancer


The FDA has granted a priority review designation to a supplemental biologics license application for a new 4-week, fixed-dose regimen as treatment in approved indications of non–small cell lung cancer and bladder cancer.

Dave Fredrickson

The FDA has granted a priority review designation to a supplemental biologics license application (sBLA) for a new 4-week, fixed-dose regimen of durvalumab (Imfinzi) as treatment in approved indications of non–small cell lung cancer (NSCLC) and bladder cancer, according to AstraZeneca, the drug developer.1

If approved by the regulatory agency, the agent can be given via intravenous infusion every 4 weeks, at a fixed dose of 1500 mg in patients with unresectable stage III NSCLC following chemoradiation therapy and previously treated patients with bladder cancer, consistent with the approved dosing in extensive-stage small cell lung cancer (ES-SCLC).

If the new dosage is approved, it will serve as an alternative option to the currently approved, weight-based dosing of 10 mg/kg given every 2 weeks. The sBLA was based on findings from several clinical trials with the agent, including data from the pivotal phase 3 CASPIAN trial (NCT03043872).

Under the Prescription Drug User Fee Act, the FDA will make a decision on the sBLA during the fourth quarter of 2020.

“The new less-frequent dosing option for NSCLC and bladder cancer will simplify and improve treatment by enabling continuity for care while minimizing the risk of exposure to infection in the healthcare setting,” Dave Fredrickson, executive vice president of the Oncology Business Unit of AstraZeneca, stated in a press release. “This takes on particular urgency during the current pandemic, as doctors care for patients at high risk of COVID-19 complications. We are working with health authorities in the United States and other countries to bring the option of 4-week, fixed dosing for [durvalumab] to patients around the world as soon as we can.”

In March 2020, the FDA approved durvalumab for use in combination with standard-of-care chemotherapy including etoposide plus either carboplatin or cisplatin (EP) in the frontline treatment of adult patients with ES-SCLC based on data from CASPIAN.

Results showed that when the PD-L1 inhibitor was added to chemotherapy, it led to a 27% reduction in the risk of death versus chemotherapy alone (HR, 0.73; 95% CI, 0.591-0.909; P = .0047).2 An improvement in median overall survival (OS) was also observed in the durvalumab arm compared with the control arm, at 13.0 months (95% CI, 11.5-14.8) versus 10.3 months (95% CI, 9.3-11.2).

In the CASPIAN trial, investigators examined the impact of the addition of immunotherapy to chemotherapy versus chemotherapy alone across 3 treatment arms: durvalumab plus tremelimumab and EP every 3 weeks for 4 cycles, followed by durvalumab every 4 weeks until disease progression with an additional dose of tremelimumab (D+T+EP arm); durvalumab plus EP given every 3 weeks for 4 cycles, followed by durvalumab given every 4 weeks until progressive disease (D+EP arm); and EP given every 3 weeks for up to 6 cycles, followed by prophylactic cranial irradiation per investigator’s discretion (EP arm).

In the trial, the PD-L1 inhibitor was given at a dose of 1500 mg and tremelimumab was given at a dose of 75 mg. In all arms, participants received etoposide at 80 mg/m2 to 100 mg/m2 on days 1 to 3 of each 21-day treatment cycle, with investigator’s choice of either carboplatin area under the curve 5 mg/mL to 6 mg/mL per minute or cisplatin at 75 mg/m² to 80 mg/m² given on day 1 of each cycle.3,4

The primary end point of the trial was OS, and key secondary end points included progression-free survival (PFS), objective response rate (ORR), as well as safety and tolerability. In order to be eligible for enrollment, patients had to have been treatment naïve with ES-SCLC defined as stage IV and classified as T any, N any, M1a or M1b or T 3 to 4. Notably, those asymptomatic or treated brain metastases that were stable were allowed to participate.

A total of 805 participants were randomized to 1 of the 3 arms: 268 were enrolled to the D+T+EP arm, 268 were enrolled to the D+EP arm, and 269 were enrolled to the EP arm. The median age of participants was 63 years in the D+T+EP and EP arms and 63 years in the D+EP arm. Moreover, 14.2% of patients had brain or central nervous system metastases in the D+T+EP arm versus 10.4% and 10.0% in the D+EP and EP arms, respectively. Patients with liver metastases accounted for 43.7%, 40.3%, and 38.7% of those on the D+T+EP, D+EP, and EP arms, respectively.

Updated results from the trial presented during the 2020 ASCO Virtual Scientific Program showed that at a median follow-up of 25.1 months, the median OS with D+EP was 12.9 months (95% CI, 11.3-14.7) versus 10.5 months (95% CI, 9.3-11.2) with EP alone (HR, 0.75; 95% CI, 0.62-0.91; P = .0032). Notably, the OS favored durvalumab regardless of whether carboplatin (HR, 0.79; 95% CI, 0.63-0.98) or cisplatin (HR, 0.67; 95% CI, 0.46-0.97) was used.

The OS rates at 18 months were highest in the D+EP arm, at 32.0%, followed by 30.7% in the D+T+EP arm, and 24.8% in the EP arm; at 24 months, the OS rates were 22.2%, 23.4%, and 14.4%, respectively.

Additionally, the D+T+EP regimen was not found to show statistically significant improvement in other investigator-assessed measures, either, per RECIST v1.1 criteria. In the D+T+EP group, the median PFS was 4.9 months (95% CI, 4.7-5.9) versus 5.4 months (95% CI, 4.8-6.2) in the EP group (HR, 0.84; 95% CI, 0.70-1.01). Moreover, the confirmed ORR in the D+T+EP group was 58.4% versus 58.0% in the EP group; the median duration of response (DOR) was 5.2 months versus 5.1 months, respectively.

The PFS for the D+EP arm compared with the EP arm was not formally examined for statistical significance. However, the median PFS with D+EP was 5.1 months (95% CI, 4.7-6.2) compared with 5.4 months (95% CI, 4.8-6.2) with EP (HR, 0.80; 95% CI, 0.66-0.96). In the D+EP and EP arms, the ORRs were 67.9% and 58.0%, respectively (odds ratio, 1.53; 95% CI, 1.08-2.18). The median DOR was 5.1 months in both treatment arms.

With regard to safety, the data proved to be consistent with what has already been reported with the agents used in all regimens analyzed. The rate of grade 3/4 adverse effects (AEs) in the D+T+EP arm was 70.3%, and the rate of serious AEs was 45.5%; these rates were 62.8% versus 36.5%, respectively, in the EP arm.

Moreover, 21.4% of those on the D+T+EP group had AEs that resulted in treatment discontinuation compared with 10.2% of those in the D+EP group and 9.4% of those in the EP group. Twelve deaths attributed to treatment-related AEs were reported in the D+T+EP cohort, along with 6 in the D+EP cohort, and 2 in the EP cohort.

Durvalumab is approved for use in the curative-intent setting of unresectable, stage III NSCLC following chemoradiation treatment in the United States, Japan, China, Europe, and other countries based on data from the pivotal phase 3 PACIFIC trial. The PD-L1 inhibitor is also approved for use in previously treated patients with advanced bladder cancer in the United States and other countries.

The agent also has approval in the United States and is under review in Japan and other countries for use in patients with ES-SCLC. Durvalumab was recently recommended for marketing authorization in the European Union for the ES-SCLC indication.


  1. Imfinzi granted FDA priority review for less-frequent, fixed-dose use. News release. AstraZeneca. August 18, 2020. Accessed August 18, 2020. https://bit.ly/3g6gUYP.
  2. L. Paz-Ares, Y. Chen, N. Reinmuth, et al. Overall survival with durvalumab plus etoposide-platinum in first-line extensive-stage SCLC: results from the CASPIAN study. Presented at: IASLC 20th World Conference on Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract OA02.02.
  3. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): updated results from the phase III CASPIAN study. J Clin Oncol. 2020;38(suppl 15):9002. doi:10.1200/JCO.2020.38.15_suppl.9002
  4. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939. doi:10.1016/S0140-6736(19)32222-6
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