Clinical trialPhase 3Lung cancer

Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer

N Engl J Med · 2024730 patients (264 durvalumab, 200 durvalumab–tremelimumab, 266 placebo)

Cheng Y, Spigel DR, Cho BC, Laktionov KK, Fang J, Chen Y, et al. N Engl J Med. 2024. 391:1313-1327

Study type: Clinical trial
Study name: ADRIATIC
Phase: Phase 3
Design: Three-arm randomised, double-blind, placebo-controlled trial
Sample size: 730 patients (264 durvalumab, 200 durvalumab–tremelimumab, 266 placebo)
Source: N Engl J Med · 2024
Trial registration: NCT03703297

In plain words

In small-cell lung cancer that is only in the chest (limited stage), the main treatment is chemotherapy and radiotherapy given together. This study showed that if the immunotherapy drug durvalumab is then given by infusion every 4 weeks for up to 2 years, the median survival rises from about 33 months to about 56 months, without a notable increase in severe side effects.

Key results

55.9 vs 33.4 months

Median overall survival

HR for death 0.73; 98.321% CI 0.54–0.98; P=0.01

16.6 vs 9.2 months

Median progression-free survival

HR 0.76; 97.195% CI 0.59–0.98; P=0.02

Drugs in this study:Carboplatin (Paraplatin)Cisplatin (Platinol)Etoposide Durvalumab (Imfinzi)

Dose and schedule cards

Concurrent chemoradiotherapy followed by durvalumab (ADRIATIC)

Limited-stage SCLC (stage I to III; stage I–II only if inoperable) without progression after concurrent chemoradiotherapyOn the page “Lung cancer” · Small cell lung cancer: first-line

Limited-stage SCLC (stage I to III; stage I–II only if inoperable) without progression after concurrent chemoradiotherapy

Drug	Dose	Route	Schedule
Concurrent chemoradiotherapy: 4 cycles of 21 days
Cisplatin or carboplatin	80 mg/m² or AUC 5	IV	Day 1
Etoposide	100 mg/m²	IV	Days 1, 2 and 3
Thoracic radiotherapy	45 Gy twice daily over 3 weeks, or 60 to 66 Gy once daily over 6 weeks	—	Concurrent with chemotherapy; starting on day 1 of cycle 1 or 2
Consolidation
Durvalumab	1500 mg (body weight less than 30 kg: 20 mg/kg)	IV (60 min)	Every 4 weeks; start within 42 days after chemoradiotherapy

Cycle length: Chemotherapy every 21 days; durvalumab every 28 days
Duration: Durvalumab for a maximum of 24 months, or until progression or intolerable toxicity

Source: FDA label for durvalumab (description of the ADRIATIC trial); trial. The dose and timing of the concurrent chemotherapy and the start of radiotherapy are from the CALGB 30610 trial. Prophylactic cranial irradiation (PCI) after chemoradiotherapy was allowed at the physician’s discretion. Pneumonitis: 14% vs 6% with placebo.

On the page “Lung cancer” · Small cell lung cancer: first-line

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Durvalumab

Durvalumab 1500 mg IV every 4 weeks (for the first 4 doses together with an IV saline placebo), then durvalumab 1500 mg every 4 weeks; continued until progression, unacceptable toxicity or a maximum of 24 months. Started within 42 days after the end of chemoradiotherapy (264 patients). FDA label for weight <30 kg: 20 mg/kg every 4 weeks.

2Durvalumab + tremelimumab

Durvalumab 1500 mg IV + tremelimumab 75 mg IV every 4 weeks for 4 doses, then durvalumab 1500 mg every 4 weeks (first single-agent dose 4 weeks after the last combination dose) for up to a maximum of 24 months (200 patients; results for this group are still blinded).

3Placebo

Two IV saline placebos every 4 weeks for 4 doses, then one placebo every 4 weeks for up to a maximum of 24 months (266 patients).

Source of the regimen details: ClinicalTrials.gov NCT03703297 (description of the arms) and the FDA label for Imfinzi (DailyMed, sections 2.2 and 14.2, September 2026 version); consistent with the abstract of the paper

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with limited-stage small-cell lung cancer (stage I to III according to the AJCC 8th edition; stage I/II had to be medically inoperable), ECOG/WHO 0 or 1, without progression after concurrent chemoradiotherapy comprising 4 cycles of platinum-based chemotherapy and radiotherapy of 60 to 66 Gy once daily over 6 weeks or 45 Gy twice daily over 3 weeks, completed within 42 days before the first dose. Prophylactic cranial irradiation (PCI) was allowed at the investigator's discretion (it had to be completed within the preceding 42 days). Exclusion criteria: active or prior autoimmune disease within the past 5 years, a history of grade ≥2 pneumonitis, active ILD, active tuberculosis, hepatitis B or C or HIV, and mixed SCLC/NSCLC histology.

Endpoints

Dual primary endpoints: overall survival and progression-free survival (blinded independent central review, RECIST 1.1) for durvalumab versus placebo. This paper is the first planned interim analysis.

Safety and side effects

Maximum grade 3 or 4 adverse events: 24.4% with durvalumab versus 24.2% with placebo. Discontinuation due to adverse events 16.4% versus 10.6%, and death due to adverse events 2.7% versus 1.9%. Grade 3 or 4 pneumonitis or radiation pneumonitis in 3.1% versus 2.6%. According to the FDA label: serious adverse events 30% in the durvalumab group (pneumonitis or radiation pneumonitis 12%, pneumonia 5%); median exposure 9.2 months.

Clinical significance and place in guidelines

ADRIATIC was the first meaningful therapeutic advance in limited-stage small-cell lung cancer in decades and led to FDA approval of consolidation durvalumab (December 2024). Durvalumab after concurrent chemoradiotherapy is now the standard of care for these patients in international guidelines.

Limitations

This is an interim analysis, and the results of the durvalumab–tremelimumab group have not yet been published; patients treated with sequential chemoradiotherapy were not enrolled; discontinuation due to adverse events was more frequent in the durvalumab group.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.