September 18, 2021: “Updated results from the CASPIAN Phase III trial showed AstraZeneca’s Imfinzi (durvalumab) in combination with a choice of chemotherapies, etoposide plus either carboplatin or cisplatin, demonstrated a sustained, clinically meaningful overall survival (OS) benefit at three years for adults with extensive-stage small cell lung cancer (ES-SCLC) treated in the 1st-line setting.
These data, which show the longest survival update ever reported for an immunotherapy treatment in this setting, were presented during a mini-oral session on 18 September 2021 at the European Society of Medical Oncology (ESMO) Congress 2021.
The CASPIAN trial met the primary endpoint of OS in June 2019, reducing the risk of death by 27% (based on a hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.59-0.91; p=0.0047), which has formed the basis of regulatory approvals in many countries around the world.
Updated results were previously presented during the ASCO20 Virtual Scientific Program in May 2020 with a median follow up of more than two years.
The latest results for Imfinzi plus chemotherapy showed sustained efficacy after a median follow up of more than three years for censored patients, with a 29% reduction in the risk of death versus chemotherapy alone (based on an HR of 0.71; 95% CI 0.60-0.86; nominal p=0.0003). Updated median OS was 12.9 months versus 10.5 for chemotherapy.
The results included a planned exploratory analysis, where an estimated 17.6% of patients treated with Imfinzi plus chemotherapy were alive at three years, versus 5.8% of patients treated with chemotherapy alone.
The survival benefits were consistent across all subgroups, in line with previous analyses.
Luis Paz-Ares, MD, PhD, Chair, Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain and principal investigator in the CASPIAN Phase III trial said: “Patients with extensive-stage small cell lung cancer historically have had limited treatment options and still face a dire prognosis, which makes these data showing that three times as many patients survive three years following Imfinzi treatment especially meaningful.
These results reinforce Imfinzi plus platinum chemotherapy as an important standard of care in this setting.”
Susan Galbraith, Executive Vice President, Oncology R&D, said: “This remarkable improvement in survival is an unprecedented achievement at three years for patients with extensive-stage small cell lung cancer.
We are deeply committed to helping improve survival rates in this disease with research into new treatment options to transform outcomes at various stages, not only with the CASPIAN trial, but also with the ADRIATIC trial in limited-stage disease.”
Imfinzi plus chemotherapy continued to demonstrate a well-tolerated safety profile consistent with the known profiles of these medicines.
Results showed 32.5% of patients experienced a serious adverse event (all causality) with Imfinzi plus chemotherapy versus 36.5% with chemotherapy alone.
Imfinzi in combination with etoposide and either carboplatin or cisplatin is approved in the 1st-line setting of ES-SCLC in more than 55 countries, including the US, Japan, China and across the EU.
Imfinzi is also being tested following concurrent chemoradiation therapy (CRT) in patients with limited-stage SCLC in the ADRIATIC Phase III trial as part of a broad development programme.
In addition, Imfinzi is also approved to treat non-small cell lung cancer (NSCLC) in the curative-intent setting of unresectable, Stage III disease after CRT in the US, Japan, China, across the EU and in many other countries, based on results from the PACIFIC Phase III trial.
Small cell lung cancer
Lung cancer is the leading cause of cancer death among men and women and accounts for about one-fifth of all cancer deaths.
Lung cancer is broadly split into NSCLC and SCLC, with about 15% classified as SCLC.
SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy.
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.
Prognosis is particularly poor, as prior to the approval of immunotherapy regimens for ES-SCLC, only 7% of all patients with SCLC and only 3% of patients with extensive-stage disease will be alive five years after diagnosis.
CASPIAN
CASPIAN was a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of 805 patients with ES-SCLC.
The trial compared Imfinzi in combination with chemotherapy (etoposide and either carboplatin or cisplatin), or Imfinzi and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone.
In the two experimental arms, patients were treated with four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional prophylactic cranial irradiation.
The trial was conducted in more than 200 centres across 23 countries, including the US, Europe, South America, Asia and the Middle East. The primary endpoint was OS in each of the two experimental arms.
In June 2019, AstraZeneca announced the CASPIAN Phase III trial had met one primary endpoint of demonstrating OS for Imfinzi plus chemotherapy at a planned interim analysis.
In March 2020, however, it was announced that the second experimental arm with tremelimumab did not meet its primary endpoint of OS.
Imfinzi
Imfinzi (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 tumour’s immune-evading tactics and releasing the inhibition of immune responses.
In addition to approvals in ES-SCLC and unresectable, Stage III NSCLC, Imfinzi is approved for previously treated patients with advanced bladder cancer in several countries. Since the first approval in May 2017, more than 100,000 patients have been treated with Imfinzi.”
