FDA Approves Imfinzi-Chemo Combo to Treat Advanced SCLC

The U.S. Food and Drug Administration (FDA) has approved Imfinzi (durvalumab), in combination with standard chemotherapy, as an initial treatment of people with extensive-stage small cell lung cancer (SCLC).

This decision was based on findings from the CASPIAN Phase 3 trial (NCT03043872), in which the combination was found to be better than standard chemo alone at extending the lives of newly diagnosed patients with extensive-stage, or widely spread, SCLC.

Adding Imfinzi, marketed by AstraZeneca, to standard care also increased responses to treatment.

“The US approval of Imfinzi brings a new medicine to extensive-stage small cell lung cancer patients in urgent need of new options,” Dave Fredrickson, executive vice president at AstraZeneca’s Oncology Business Unit, said in a press release.

“Imfinzi is the only immunotherapy to show both a significant survival benefit and improved response rate in combination with chemotherapy for these patients, an important step forward in treating this devastating disease,” Fredrickson added.

Imfinzi is an immune checkpoint inhibitor designed to harness the immune response by blocking PD-L1, a protein involved in mechanisms used by cancer cells to evade immune system attack.

The ongoing CASPIAN trial is investigating the benefits of Imfinzi plus standard first-line chemotherapy to treat newly diagnosed SCLC patients whose cancer has spread in the lungs or to other parts in the body.

It is being conducted in more than 200 centers in 23 countries, including the U.S., Europe, South America, Asia, and the Middle East.

CASPIAN enrolled 805 patients, who were randomly assigned to either standard chemotherapy alone (etoposide plus cisplatin or carboplatin) — serving as a control group — or to the combination of Imfinzi and standard chemotherapy.

Imfinzi-treated patients completed four cycles of chemotherapy, while controls received up to six such cycles plus optional prophylactic cranial irradiation, a form of radiation therapy.

Its primary aim was to determine if the Imfinzi combo extended patients’ lives compared to chemo only. Secondary goals included the time patients lived without disease worsening, the proportion of patients responding to treatment, and changes in symptoms and quality of life. Safety and tolerability were also assessed.

Results revealed that Imfinzi extended median overall survival from 10.3 to 13.0 months — corresponding to a 27% reduction in the risk of death. At 18 months, 34% of Imfinzi-treated patients were alive, as were 25% of those in the control group.

Imfinzi also increased the percentage of patients responding to treatment (68% vs. 58%), as well those showing a durable response at one year (23% vs. 6%).

The safety and tolerability of the Imfinzi combination was consistent with previous studies. Severe and life-threatening adverse events, as well as treatment discontinuations, were similar in both groups.

“Patients with extensive-stage small cell lung cancer continue to face a poor prognosis, and finding new medicines to improve outcomes in this setting has been a formidable challenge,” said Jonathan Goldman, MD, a lead investigator in CASPIAN.

“The CASPIAN trial enables clinicians to choose durvalumab [Imfinzi] in combination with etoposide and either carboplatin or cisplatin, making this an important new 1st-line treatment option for patients that is both effective and well-tolerated,” added Goldman, a professor at the University of California, Los Angeles.

An additional group of people in the CASPIAN trial were treated with Imfinzi plus chemotherapy and tremelimumab, an experimental immunotherapy that activates the immune system by blocking the CTLA-4 protein. Findings from this part — to be detailed at an upcoming medical conference — showed that adding tremelimumab did not further benefit patients.

Imfinzi is also approved in the U.S. to treat another form of lung cancer, called non-small cell lung cancer, and for advanced forms of bladder cancer.

Regulatory authorities in the European Union and Japan are also reviewing the Imfinzi–standard chemo combination for extensive-stage SCLC patients, which was first approved in Singapore.

Another Phase 3 trial, called ADRIATIC (NCT03703297), is testing Imfinzi after chemoradiation therapy in patients with limited-stage SCLC (generally, cancer limited to one lung and possibly in lymph nodes on one side of chest).

This study is enrolling eligible patients worldwide; more information can be found here. It is expected to end in February 2024.