On June 2, 2024 Astrazeneca reported positive results from the ADRIATIC Phase III trial showed ​Imfinzi (durvalumab) ​demonstrated statistically significant and clinically meaningful improvements in the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to placebo for patients with limited-stage small cell lung cancer (LS-SCLC) who had not progressed following standard-of-care concurrent chemoradiotherapy (cCRT) (Press release, AstraZeneca, JUN 2, 2024, View Source [SID1234643933]).

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These results will be presented today during the Plenary Session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (abstract #LBA5).

Results from the planned interim analysis showed Imfinzi reduced the risk of death by 27% versus placebo (based on an OS hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.57-0.93; p=0.0104). Estimated median OS was 55.9 months for Imfinzi versus 33.4 months for placebo. An estimated 57% of patients treated with Imfinzi were alive at three years compared to 48% on placebo. Imfinzi also reduced the risk of disease progression or death by 24% (based on a PFS HR of 0.76; 95% CI 0.61-0.95; p=0.0161) versus placebo. Median PFS was 16.6 months for Imfinzi versus 9.2 months for placebo. An estimated 46% of patients treated with Imfinzi had not experienced disease progression at two years compared to 34% on placebo.

The OS and PFS benefits observed were generally consistent across key prespecified patient subgroups including age, sex, race, disease stage1 at diagnosis, prior radiation and whether patients received prophylactic cranial irradiation.

David R. Spigel, MD, Chief Scientific Officer at Sarah Cannon Research Institute and investigator in the trial, said: "The ADRIATIC results represent a breakthrough in limited-stage small cell lung cancer, a highly aggressive disease where recurrence rates are high and only 15 to 30 per cent of patients survive five years. Durvalumab is the first systemic treatment to show improved survival for these patients in decades and should become a new standard of care in this setting."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "The strong improvement in overall survival seen with Imfinzi after concurrent chemoradiotherapy is transformative in the treatment of limited-stage small cell lung cancer. These tremendous results underscore our ambition to drive up survival rates in this earlier-stage lung cancer setting, and we look forward to working with regulatory authorities to bring Imfinzi to these patients as quickly as possible."

Summary of results: ADRIATIC

​

​Imfinzi

​(n=264)

​Placebo

​(n=266)

OS

Median OS, in months (95% CI)

55.9

(37.3-NEi)

33.4

(25.5-39.9)

Hazard ratio (95% CI)

0.73 (0.57-0.93)

p-value

0.0104

OS rate at 24 months (%)

68.0

58.5

OS rate at 36 months (%)

56.5

47.6

PFS

Median PFS, in months (95% CI)

16.6

(10.2-28.2)

9.2

(7.4-12.9)

Hazard ratio (95% CI)

0.76 (0.61-0.95)

p-value

0.0161

PFS rate at 18 months (%)

48.8

36.1

PFS rate at 24 months (%)

46.2

34.2

​i Not estimable

The safety profile for Imfinzi was generally manageable and consistent with the known profile of this medicine. No new safety signals were observed. Grade 3 and 4 adverse events due to any cause occurred in 24.4% of patients treated with Imfinzi and 24.2% of patients treated on placebo.

Notes

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.2 Lung cancer is broadly split into non-small cell lung cancer and SCLC, with about 15% of cases classified as SCLC, a highly aggressive form of the disease.3-4

LS-SCLC (Stage I-III), which accounts for approximately 30% of SCLC diagnoses, is classified as SCLC that is generally only in one lung or one side of the chest.5-6 LS-SCLC typically recurs and progresses rapidly despite initial response to standard-of-care chemotherapy and radiotherapy.4,7 The prognosis for LS-SCLC is particularly poor, as only 15-30% of patients will be alive five years after diagnosis.8

ADRIATIC
The ADRIATIC trial is a randomised, double-blind, placebo-controlled, multi-centre global Phase III trial evaluating Imfinzi monotherapy and Imfinzi plus Imjudo (tremelimumab) versus placebo in the treatment of 730 patients with LS-SCLC who had not progressed following cCRT. In the experimental arms, patients were randomised to receive a 1500mg fixed dose of Imfinzi with or without Imjudo 75mg every four weeks for up to four doses/cycles each, followed by Imfinzi every four weeks for up to 24 months.

The dual primary endpoints were PFS and OS for Imfinzi monotherapy versus placebo. Key secondary endpoints included OS and PFS for Imfinzi plus Imjudo versus placebo, safety and quality of life measures. The trial included 164 centres in 19 countries across North and South America, Europe and Asia.

Imfinzi 
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is currently approved in a number of countries across multiple types of lung cancer. Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiation therapy. Imfinzi is also approved for the treatment of extensive-stage SCLC and in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC.

In addition to its indications in lung cancers, Imfinzi is approved in a number of countries in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU and in previously treated patients with advanced bladder cancer in a small number of countries.

Since the first approval in May 2017, more than 220,000 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 SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal cancers and other solid tumours.