Durvalumab Shows Statistically-significant Benefit in Aggressive Lung Cancer

Lung radiography | Doctor examining a lung radiography
Lung radiography | Doctor examining a lung radiography

Positive overall survival (OS) results from the Phase III CASPIAN trial with durvalumab (Imfinzi®; AstraZeneca) in 1st-line extensive-stage small cell lung cancer (SCLC), a disease with significant unmet need and limited treatment options for patients, were presented earlier toady.

Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths. [1] Lung cancer is broadly split into NSCLC and SCLC, with about 15% classified as SCLC. [2] About two-thirds of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body. [3] SCLC is an aggressive, fast-growing cancer that recurs and progresses rapidly despite initial response to platinum-based chemotherapy. [4] Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis. [3]

New treatment option
Durvalumab is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.

As part of a broad development program, durvalumab is also being tested as a monotherapy and in combination with tremelimumab, a human monoclonal antibody and potential new medicine that targets and blocks the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), as a treatment for patients with NSCLC, small cell lung cancer, bladder cancer, head and neck cancer, liver cancer, cervical cancer, biliary tract cancer and other solid tumors.

Interim analysis
A planned interim analysis conducted by an Independent Data Monitoring Committee concluded that the trial has met its primary endpoint by showing a statistically-significant and clinically-meaningful improvement in OS in patients treated with durvalumab in combination with standard-of-care etoposide and platinum-based chemotherapy options vs. chemotherapy alone.

The safety and tolerability for this combination with durvalumab was consistent with the known safety profiles of these medicines. The results will be presented during an upcoming medical society meeting.

New hope
“The Phase III CASPIAN results offer new hope for patients who are facing the devastating diagnosis of small cell lung cancer, and for whom new medicines are urgently needed,” noted José Baselga, Executive Vice President, Oncology R&D at AstraZeneca.

“This is the first trial offering the flexibility of combining immunotherapy with different platinum-based regimens in small cell lung cancer, expanding treatment options,” he concluded.

The CASPIAN trial is a randomised, open-label, multi-centre, global, Phase III study of durvalumab plus platinum-based chemotherapy options or the combination of durvalumab, tremelimumab and chemotherapy vs. chemotherapy alone as a 1st-line treatment for patients with extensive-stage SCLC. The trial will continue to the final analysis of OS for the combination of dual immune checkpoint blockade with chemotherapy.

This combination includes tremelimumab, an anti-CTLA4 antibody and potential new medicine, with durvalumab, an anti-PDL1 antibody, and chemotherapy.

In the experimental arms, patients were treated with up to four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and prophylactic cranial irradiation.

The trial is being conducted in more than 200 centers across 22 countries, including the US, Europe, South America, Asia and the Middle East. The primary endpoint is OS.

Clinical trial
Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN) – NCT03043872

Reference
[1] World Health Organization. International Agency for Research on Cancer. Online [Article]. Last Accessed June 27, 2019.
[2] LUNGevity Foundation. Types of Lung Cancer. Online. [Article]. Last Available at . Accessed June 27, 2019.
[3] Cancer.Net. Lung Cancer – Small Cell. Online. [Article]. Last Accessed June 27, 2019.
[4] Kalemkerian GP, et al. Treatment Options for Relapsed Small-Cell Lung Cancer: What Progress Have We Made? Journal of Oncology Practice, volume 14, issue no. 6 (June 1 2018) 369-370.