AstraZeneca's Imfinzi Significantly Improves Overall Survival in First-Line Extensive-Stage Small Cell Lung Cancer in Phase III CASPIAN Trial

September 10, 2019 /Bio ValleyBIOON/ -- The 20th World Conference on Lung Cancer (WCLC), hosted by the International Association for the Study of Lung Cancer (IASLC) in 2019, was held in Barcelona, Spain, from September 7 to 10. ThisConferenceabove,AstraZeneca(AstraZeneca) announced PD-L1TumorDetailed Data from the Phase III CASPIAN Clinical Study of First-Line Immunotherapy with Imfinzi (durvalumab) for Extensive-Stage Small Cell Lung Cancer (ES-SCLC). The results demonstrated that fixed-dose Imfinzi combined with standard-of-care (SoC) platinum-based chemotherapy significantly improved overall survival (OS) compared to SoC platinum-based chemotherapy alone.

SCLC is an aggressive, fast-growing cancer that, despite an initial response to platinum-based chemotherapy, rapidly relapses and progresses. Based on these study results, Imfinzi is the first to demonstrate a survival benefit and improved durable responses in patients with ES-SCLC.TumorImmunotherapy.

CASPIAN is a randomized, open-label, multicenter, global Phase III study comparing the efficacy and safety of Imfinzi plus standard-of-care (SoC) platinum-based chemotherapy (etoposide plus cisplatin or carboplatin), Imfinzi plus tremelimumab plus SoC platinum-based chemotherapy, and SoC platinum-based chemotherapy alone as first-line treatment in patients with extensive-stage small cell lung cancer (ES-SCLC). The Imfinzi plus tremelimumab plus SoC platinum-based chemotherapy regimen is a dual immune checkpoint blockade combined with chemotherapy, consisting of the CTLA-4 checkpoint inhibitor tremelimumab (an anti-CTLA-4 monoclonal antibody), the PD-L1 checkpoint inhibitor Imfinzi (an anti-PD-L1 monoclonal antibody), and SoC chemotherapy. In the study, patients in the experimental arms received up to four cycles of SoC chemotherapy, while those in the control arm were allowed up to six cycles of SoC chemotherapy and prophylactic cranial irradiation (PCI). The study was conducted at more than 200 clinical centers across 22 countries, including the United States, Europe, South America, Asia, and the Middle East. The primary endpoint was overall survival (OS).

An interim analysis conducted by the Independent Data Monitoring Committee (IDMC) concluded that the study had met its primary endpoint, demonstrating that compared with the standard-of-care (SoC) chemotherapy group, the Imfinzi plus SoC chemotherapy group had a 27% reduction in the risk of death (HR=0.73, 95% CI: 0.591–0.909, p=0.0047), significantly prolonged overall survival (median OS: 13.0 months [11.5, 14.8] vs. 10.3 months [9.3, 11.2]), and a substantially higher 18-month survival rate (33.9% vs. 24.7%).

Furthermore, across all efficacy endpoints, the Imfinzi + SoC chemotherapy group demonstrated therapeutic benefits compared with the SoC chemotherapy alone group, including a significantly higher progression-free survival rate at 12 months (PFS rate: 17.5% vs. 4.7%), a 10.3 percentage-point increase in confirmed objective response rate at 12 months (ORR: 67.9% vs. 57.6%), and a higher proportion of patients with sustained duration of response (DOR) at 12 months (DOR: 22.7% vs. 6.3%). In this study, the safety and tolerability profile of the Imfinzi + SoC chemotherapy regimen was consistent with that observed in prior studies. Grade 3 or 4 adverse events occurred in 61.5% of patients in the Imfinzi + SoC treatment group and 62.4% in the SoC chemotherapy group, with similar proportions of patients discontinuing treatment due to adverse events in both groups (9.4% vs. 9.4%).

Currently, Imfinzi is also being evaluated in another Phase III clinical trial, ADRIATIC, which assesses the use of Imfinzi following concurrent chemoradiotherapy (CCRT) in patients with limited-stage small cell lung cancer (SCLC).

AstraZenecaTumorJose Baselga, Executive Vice President of Research and Development, stated: “The results from the Phase III CASPIAN study are highly encouraging, with more than one-third of patients with small cell lung cancer (SCLC) treated with Imfinzi plus standard-of-care (SoC) chemotherapy still alive at the 18-month milestone. Given the aggressive nature of this disease, these findings are significant. Notably, these results may guide physicians in selecting Imfinzi in combination with cisplatin or carboplatin as the chemotherapy backbone. We look forward to collaborating with regulatory authorities to make Imfinzi available to SCLC patients worldwide as soon as possible.”

Principal Investigator of the CASPIAN Study, University Hospital October 12th, Madrid, SpainTumorDr. Luis Paz Ares stated, “Treatment options for patients with SCLC are limited; it is a devastating disease with a 5-year survival rate of less than 6%. The robust efficacy data from the CASPIAN study demonstrate that Imfinzi in combination with four cycles of chemotherapy provides a significant survival benefit compared to up to six cycles of chemotherapy and prophylactic cranial irradiation (PCI). These data provide evidence and hope for new treatment options for patients with SCLC.”

Lung cancer is the leading cause of cancer-related deaths in both men and women, accounting for approximately one-fifth of all cancer deaths. Lung cancer is broadly classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with SCLC comprising about 15%. Approximately two-thirds of patients with SCLC areDiagnosisExtensive-stage disease, meaning the cancer has spread widely throughout the lungs or metastasized to other parts of the body. SCLC is an aggressive, rapidly growing cancer that, although initially responsive to platinum-based chemotherapy, tends to recur and progress quickly. The prognosis is particularly poor, with only 6% of SCLC patients surviving five years after diagnosis.

Imfinzi is a PD-L1 immunotherapy that targets and binds to programmed death-ligand 1 (PD-L1), blocking the interaction of PD-L1 with PD-1 and CD80, thereby combatingTumorimmune evasion strategies and release the suppression of immune responses.

In the field of lung cancer, to date, Imfinzi has been approved in more than 49 countries worldwide (including the United States, the European Union, and Japan) for the treatment of patients with unresectable locally advanced (Stage III) non-small cell lung cancer (NSCLC). This approval is based on data from the Phase III PACIFIC study. Earlier this month, at the American ClinicalTumorThe 3-year overall survival (OS) data presented at the American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated durable and sustained OS benefits in patients with unresectable stage III non-small cell lung cancer (NSCLC) who did not experience disease progression following concurrent chemoradiotherapy (CRT): the 3-year OS rate was 57% in the Imfinzi group, with median OS not yet reached, compared to 43.5% and 29.1 months, respectively, in the placebo group. Based on these results, Imfinzi became the first immunotherapy proven to confer a 3-year survival benefit in the population with unresectable stage III NSCLC.

Currently, AstraZeneca is conducting a large clinical program to evaluate Imfinzi as monotherapy and in combination with tremelimumab and other agents for NSCLC, SCLC, bladder cancer, head and neck cancer,Liver Cancer, cervical cancer, biliary tract cancer, and other solid tumors. (Bioon.com)

Original Source:Imfinzi is first immunotherapy to show both significant survival benefit and improved, durable responses in extensive-stage small cell lung cancer