AstraZeneca gets a green light on Imfinzi for small-cell lung cancer — setting the stage for a battle with Roche's Tecentriq
The standard-of-care for small-cell lung cancer (SCLC) for decades was platinum-based chemotherapy, but that paradigm shifted in 2018, with the approval of Bristol Myers Squibb’s checkpoint inhibitor Opdivo in the second-line setting. Since then, a slate of immunotherapies have secured SCLC approvals, and the latest is AstraZeneca’s flagship Imfinzi, which was approved on Monday in combination with standard chemotherapy as the first line of defense in extensive-stage SCLC patients.
The approval was based on the results of the late-stage, 805 patient-CASPIAN trial, which tested Imfinzi plus standard-of-care chemotherapy, or Imfinzi and chemotherapy with the addition of AstraZeneca’s in-house CTLA-4 drug tremelimumab, versus chemotherapy alone.
The primary endpoint was overall survival in each of the two experimental arms. The combination of Imfinzi and chemotherapy cut the risk of death by 27% (HR: 0.73; p=0.0047). Patients on the Imfinzi arm lived a median 13 months longer, versus 10.3 months in the chemotherapy group.
The arm with tremelimumab failed to achieve the primary goal. The Imfinzi/tremelimumab combo, once touted as the cornerstone of AstraZeneca’s checkpoint development strategy, has already seen a raft of failures in the past — it did not improve overall survival in certain patients with head and neck cancer, in addition to the big flop in the keenly-watched MYSTIC non-small cell lung cancer (NSCLC) trial. Although the duo has, when combined with chemotherapy, worked in delaying disease progression in frontline cases of stage 4 NSCLC.
Roche’s Tecentriq in combination with chemotherapy was approved first-line treatment for extended stage SCLC last September, based on a 30% reduction in risk of death observed in the pivotal IMpower133 trial. Months earlier in June, Merck’s keystone checkpoint inhibitor Keytruda had scored FDA approval as a monotherapy for the treatment of SCLC patients who had progressed on or after platinum-based chemotherapy and at least one prior line of therapy.
On Monday, the FDA approved the Imfinzi plus chemotherapy combination as a first-line treatment for extended-stage SCLC patients, pitting against Tecentriq it in the exact same patient population.
Meanwhile, PharmaMar’s lurbinectedin received priority review last month for the treatment of SCLC patients who progressed on platinum therapy based on data from a single-arm, mid-stage study showing an overall response rate (ORR) of about 35%.
Lung cancer is the leading cause of cancer death globally, according to the WHO. The two main types of lung cancer are non-small cell and small cell, and NSCLC accounts for about 85% of all cases. About two-thirds of SCLC patients are diagnosed with extended stage-SCLC, in which the cancer has spread widely through the lung or to other parts of the body.