AstraZeneca has scored FDA approval in the advancement of its high-flying cancer therapy Imfinzi that comes with some controversy.
The nod allows Imfinzi to treat patients with resectable non-small cell lung cancer (NSCLC) perioperatively. In the regimen, the PD-L1 inhibitor is used in combination with chemotherapy before surgery and then as a monotherapy after surgery.
There is little doubt about the effectiveness of the treatment in the indication, as the phase 3 AEGEAN study showed that Imfinzi reduced the risk of recurrence, progression or death by 32% when compared to chemotherapy alone. But because of the design of the trial, there was no way to assess the individual contributions of the two stages of the therapy.
In an FDA advisory committee meeting three weeks ago, regulators expressed their concerns about perioperative regimens’ ramping up the risk of toxicities because of overtreatment without any additional benefit. How much is gained by using Imfinzi before surgery? How much is gained by using it after surgery? According to the experts, under the current trial design, there is no way to tell.
As a result, the panel of 11 voted unanimously to revamp the design of future perioperative clinical trials, requiring them to single out the contribution of each treatment phase.
As for the AZ application, the formidable trial results were still compelling enough to gain the nod in patients with no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. Imfinzi already has gained approval in the indication in the U.K., Switzerland and Taiwan.
“This approval brings an important new treatment option that should become a backbone combination approach for patients with resectable non-small cell lung cancer, who have historically faced high rates of recurrence even after chemotherapy and surgery,” John Heymach, M.D., Ph.D., professor and chair of thoracic/head and neck medical oncology at the University of Texas’ MD Anderson Cancer Center, said in AZ’s release.
This approval is not the first in the indication for perioperative treatment. In October of last year, the FDA signed off on Merck’s powerhouse Keytruda to treat early NSCLC patients on both sides of surgery.
Both Keytruda and Imfinzi could eventually be surpassed in the indication by Bristol Myers Squibb’s Opdivo. In the CheckMate-816 trial, the BMS blockbuster tallied a 37% risk reduction figure—even though the combo was used along with chemotherapy only before surgery.
Opdivo also is up for potential approval in October based on a trial that showed its perioperative use provided a 42% reduction in the risk of tumor recurrence, progression or death in patients with stage 2 to 3b NSCLC.
There are an estimated 2.4 million people diagnosed with lung cancer each year, with approximately 235,000 expected in the U.S. in 2024. About 25% to 30% of all patients with NSCLC—the most common form of lung cancer—are diagnosed early enough to have surgery, but the majority will develop recurrence, and only 36% to 46% of patients with stage 2 disease will survive for five years, AZ said.
The nod is another boost for fast-rising Imfinzi. Earlier on Thursday, ahead of the approval, the FDA granted priority review and breakthrough therapy designations for Imfinzi to treat patients with limited-stage small cell lung cancer.
Imfinzi has been on the market for seven years, with approvals in biliary tract and endometrial cancers. It also has been endorsed for extensive-stage small cell lung cancer, unresectable stage 3 NSCLC and in combination with AZ’s Imjudo and chemotherapy for metastatic NSCLC.
Imfinzi was a blockbuster by 2019 and racked up sales of $4.2 billion last year, making it AZ’s second-most lucrative oncology drug behind Tagrisso, which generated revenue of $5.8 billion.