Imfinzi ( Durvalumab ) has been approved in the European Union for the 1st-line treatment of adults with extensive-stage small cell lung cancer ( ES-SCLC ) in combination with a choice of chemotherapies, Etoposide plus either Carboplatin or Cisplatin.
Small cell lung cancer is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy.
The approval by the European Commission was based on positive results from the phase III CASPIAN trial showing Durvalumab plus chemotherapy demonstrated a statistically significant and clinically meaningful overall survival ( OS ) benefit for the 1st-line treatment of patients with ES-SCLC.
The CASPIAN trial met the primary endpoint of overall survival 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 median overall survival of 13.0 months versus 10.3 months for chemotherapy alone.
These results were published in The Lancet in 2019.
The results have also shown an increased confirmed objective response rate ( ORR ) for Durvalumab plus chemotherapy ( 68% versus 58% for chemotherapy alone ) and that Durvalumab added to chemotherapy delayed the time for disease symptoms to worsen.
An updated analysis has recently shown sustained efficacy for Durvalumab plus chemotherapy after a median follow up of more than two years ( OS HR: 0.75; 95% CI 0.62-0.91; nominal p=0.0032 ), with median overall survival of 12.9 months versus 10.5 months for chemotherapy alone.
The safety and tolerability for Imfinzi plus chemotherapy were consistent with the known safety profile of these medicines.
No patients tested positive for treatment-emergent anti-drug antibodies to Durvalumab.
The CASPIAN trial used a fixed dose of Durvalumab ( 1500 mg ) administered every three weeks for four cycles while in combination with chemotherapy and then every four weeks until disease progression.
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 Durvalumab in combination with Etoposide and either Carboplatin or Cisplatin chemotherapy, or Durvalumab and chemotherapy with the addition of a second immunotherapy, Tremelimumab, versus chemotherapy alone.
In the 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 primary endpoint was overall survival in each of the two experimental arms.
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.
Lung cancer is the leading cause of cancer death among both men and women and accounts for about one fifth of all cancer deaths.
Lung cancer is broadly split into non-small cell lung cancer ( NSCLC ) and SCLC, with about 15% classified as SCLC.
About two thirds of SCLC patients are diagnosed with ES-SCLC, in which the cancer has spread widely through the lung or to other parts of the body. Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis. ( Xagena )
Source: AstraZeneca, 2020