FDA Approves Durvalumab for Treatment of Adults Patients With LS-SCLC

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Updated December 5 at 11:14 AM.

The FDA approved durvalumab (Imfinzi; AstraZeneca) for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed after receiving concurrent platinum-based chemotherapy and radiation therapy. This approval was based on results from the phase 3 ADRIATIC clinical trial (NCT03703297) which were presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the New England Journal of Medicine.^1,2

SCLC is a highly aggressive form of lung cancer, and for those with LS-SCLC, the prognosis is poor. Approximately 15% to 30% of patients will survive 5 years after diagnosis, and the disease will often recur and progress quickly despite initial response to standard of care chemotherapy and radiotherapy, further emphasizing a need for an effective treatment.¹

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, releasing the inhibition of immune responses. Additionally, durvalumab has approved indications as a monotherapy or in combination with other treatments in non-small cell lung cancer, biliary tract cancer, and endometrial cancer.¹

ADRIATIC (NCT03703297) is a randomized, double-blind, placebo-controlled, multicenter global phase 3 clinical trial which evaluated durvalumab monotherapy and durvalumab with tremelimumab (Imjudo; AstraZeneca) compared with placebo in patients with LS-SCLC who had not progressed following chemotherapy and radiotherapy. A total of 730 patients were enrolled and randomly assigned to receive durvalumab monotherapy (n = 264; fixed dose of 1500 mg every 4 weeks), durvalumab with tremelimumab (n = 200; 1500 mg every 4 weeks, 75 mg every 4 weeks for up to 4 doses per cycle), or placebo (n = 266; placebo every 4 weeks) for up to 24 months.^2,3

The primary end points were progression-free survival (PFS) and overall survival (OS), which were assessed at approximately 6 years. Additionally, secondary end points include objective response rate, time to death or distant metastasis, and quality of life, which were assessed at approximately 6 years. Adverse events (AEs) were considered other outcome measure.³

According to the findings, treatment with durvalumab led to significantly longer OS (median: 55.9 months, 95% CI 37.3 to not reached) compared with placebo (median: 33.4 months, 95% CI 25.5-39.9). Additionally, PFS was more favorable for those receiving durvalumab (median: 16.6 months, 95% CI 10.2-28.2) compared with placebo (median: 9.2 months, 95% CI 7.4-12.9). For patients receiving durvalumab, the risks of death and disease progression or death were reduced by approximately 27% and 24%, respectively. Approximately 57% of patients treated with durvalumab were alive at 3 years compared with 48% of those receiving placebo.^1,2

“Durvalumab is the first and only systemic treatment following curative-intent, platinum-based chemoradiotherapy to show improved survival for patients with this aggressive form of lung cancer. This finding represents the first advance for this disease in 4 decades,” Suresh Senan, PhD, professor of Clinical Experimental Radiotherapy at the Amsterdam University Medical Centers, Netherlands, said in a news release. “The ADRIATIC trial showed 57% of patients were still alive at 3 years after being treated with durvalumab, which underscores the practice-changing potential of this medicine in this setting.”¹

Approximately 24.4% and 24.2% of patients receiving durvalumab and placebo, respectively, were observed to experience AEs with a maximum grade of 3 or 4. The most common grade 3 or 4 AEs were pneumonitis or radiation pneumonitis (durvalumab: 3.1%; placebo: 2.6%). Additionally, about 16.4% and 10.6% of patients, respectively, had to discontinue treatment because of AEs. Death was observed in both the durvalumab and placebo groups, which were 2.7% and 1.9%, respectively. The investigators also noted that safety profile for durvalumab was consistent with the known profile.^1,2

“This new treatment option is a game changer for patients with limited-stage SCLC, a disease known for its high rate of recurrence. Historically, more often than not, clinical trials to identify new treatment options for this type of cancer have failed to show benefit,” Dusty Donaldson, founder and executive director of LiveLung, said in the news release. “We are therefore so excited that many more people will now have the opportunity to access this immunotherapy treatment that holds the potential to significantly improve outcomes."¹

REFERENCES

1. AstraZeneca. Imfinzi approved in the US as first and only immunotherapy regimen for patients with limited-stage small cell lung cancer. News release. December 5, 2024. Accessed December 5, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-approved-in-us-for-limited-stage-sclc.html

2. Cheng Y, Spigel DR, Cho BC, et al. Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer. NEJM. 2024;391(14):1313-1327. doi:10.1056/NEJMoa2404873

3. Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC). ClinicalTrials.gov identifier: NCT03703297. Updated November 6, 2024. Accessed December 5, 2024. https://clinicaltrials.gov/study/NCT03703297