July 19, 2021: AstraZeneca’s Imfinzi (durvalumab) has been approved in China for the 1st-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC), in combination with standard of care platinum chemotherapy (etoposide plus a choice of either carboplatin or cisplatin).
The approval by China’s National Medical Products Administration was based on positive results from the CASPIAN Phase III trial.
The trial showed that Imfinzi plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus chemotherapy alone.
In addition, results from the China cohort of patients were consistent with the global results.
Small cell lung cancer (SCLC) is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy.
Prognosis is particularly poor, as only 7% of all SCLC patients and 3% of those with extensive-stage disease will be alive five years after diagnosis.
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “Today’s approval of Imfinzi plus chemotherapy brings an important global standard of care to patients with extensive-stage small cell lung cancer in China, who have had few treatment options and a dire prognosis. Physicians can now offer these patients a well-tolerated immunotherapy regimen with sustained overall survival and prolonged treatment response, as well as convenient dosing. This is also the first time physicians have had the choice to combine immunotherapy with cisplatin, a preferred chemotherapy in this setting in China.”
The CASPIAN Phase III trial met the primary endpoint of OS for Imfinzi plus chemotherapy in June 2019, reducing the risk of death by 27% versus chemotherapy alone (based on a hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.59-0.91; p=0.0047), with a median OS of 13.0 months versus 10.3 months for chemotherapy alone. These results were published in The Lancet in October 2019.4 Results also showed an increased confirmed objective response rate for Imfinzi plus chemotherapy (68% versus 58% for chemotherapy alone). Imfinzi added to chemotherapy delayed the time for disease symptoms to worsen.4
An updated analysis showed sustained efficacy for Imfinzi plus chemotherapy after a median follow up of more than two years (OS HR of 0.75; 95% CI 0.62-0.91; nominal p=0.0032), with median OS of 12.9 months versus 10.5 months for chemotherapy alone. An estimated 22.2% of patients treated with Imfinzi plus chemotherapy were alive at 24 months versus 14.4% for chemotherapy alone. The safety and tolerability for Imfinzi and chemotherapy were consistent with the known safety profiles of these medicines. No patients tested positive for treatment-emergent anti-drug antibodies to Imfinzi.
Safety and efficacy results in the China cohort of patients were consistent with results in the overall global trial population. Detailed results from this cohort will be presented at a forthcoming medical meeting.
The CASPIAN Phase III trial used a fixed dose of Imfinzi (1500mg) administered every three weeks for four cycles while in combination with chemotherapy and then every four weeks as a monotherapy until disease progression.
Based on the trial results, 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 and across the EU.
Imfinzi is also being tested following concurrent chemoradiation therapy 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 chemoradiation therapy 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.
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.
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 etoposide and either carboplatin or cisplatin platinum chemotherapy, 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 (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.
As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, SCLC, bladder cancer, hepatocellular carcinoma, biliary tract cancer (a form of liver cancer), oesophageal cancer, gastric and gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer, and other solid tumours.”