First-line Imfinzi-Chemo Therapy Extends Survival of Patients with Aggressive Lung Cancer, Phase 3 Trial Shows

Adding the immune checkpoint inhibitor Imfinzi (durvalumab) to standard chemotherapy care significantly extends the survival of patients with untreated extensive-stage small cell lung cancer (ES-SCLC), an aggressive form of lung cancer, a Phase 3 trial shows.

The trial’s findings were presented at the Presidential Symposium of the 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer, which was held recently in Barcelona, Spain.

Imfinzi is an immune checkpoint inhibitor developed by AstraZeneca that has been approved by the U.S. Food and Drug Administration for the treatment of advanced bladder cancer and non-small cell lung cancer.

To determine if the therapy could bring some benefit when included in the first-line treatment of ES-SCLC patients, researchers at AstraZeneca designed the three-arm CASPIAN Phase 3 trial (NCT03043872).

In total, the trial included 988 patients who were randomized to receive chemotherapy only (etoposide plus cisplatin or carboplatin), a combination of Imfinzi plus chemotherapy, or Imfinzi, the investigational immunotherapy tremelimumab, and chemotherapy.

Patients treated with Imfinzi completed four cycles of chemotherapy, while those from the control group had up to six cycles of chemotherapy and optional prophylactic cranial irradiation, a form of radiation therapy to destroy cancer cells.

The trial’s primary outcome was to evaluate patients’ overall survival. Secondary outcomes included assessing the time patients lived without their disease worsening, the percentage of patients whose tumor decreased by a given amount within the study’s timeframe, and duration of response.

New findings from CASPIAN, comparing the chemotherapy group to patients receiving a combination of Imfinzi plus chemotherapy, have shown that:

• Imfinzi increased patients’ median overall survival from 10.3 to 13.0 months, corresponding to a 27% reduction in the risk of death.
• At 18-months follow-up, 33.9% of patients receiving Imfinzi in combination with chemotherapy were alive, compared with 24.7% of those in the control group.
• At 12-months follow-up, 17.5% of patients treated with Imfinzi-chemo showed no signs of disease worsening, whereas 4.7% of those treated with standard chemo achieved the same outcome.
• Imfinzi increased the percentage of patients responding to treatment (67.9% versus 57.6%), as well as the percentage of those showing a durable treatment response at 12-months follow-up (22.7% versus 6.3%).
• The safety and tolerability profile of Imfinzi in combination with chemotherapy was consistent with previous studies.
• The incidence of severe (grade 3) and life-threatening (grade 4) adverse events (61.5% in the Imfinzi group and 62.4% in the control group) and treatment discontinuations (9.4% in both groups) were similar in both treatment groups.

“We are encouraged to see more than a third of small cell lung cancer patients treated with Imfinzi plus chemotherapy alive at the 18-month landmark, which is remarkable given the aggressive nature of the disease,” José Baselga, executive vice president of oncology research and development at AstraZeneca, said in a news release.

“It is also noteworthy that these results may enable physicians to choose Imfinzi in combination with either cisplatin or carboplatin chemotherapy backbones. We look forward to working with regulatory authorities to bring Imfinzi to patients with small cell lung cancer around the world as soon as possible,” he said.

Luis Paz-Ares, MD, PhD, chair of the medical oncology department at the Hospital Universitario Doce de Octubre, in Madrid, Spain, and principal investigator of CASPIAN, added: “The significant survival benefit demonstrated with Imfinzi combined with only four cycles of a choice of chemotherapy, compared to a robust control arm, provides evidence and hope of a new treatment option for these patients.”

Besides CASPIAN, Imfinzi is also being tested in patients with limited-stage small-cell lung cancer following chemoradiation therapy in the multicenter ADRIATIC Phase 3 trial (NCT03703297), which is currently recruiting patients.