Clinical trialPhase 3Lung cancer

Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial

The Lancet · 2019537 patients in the two groups reported in this paper (268 in the durvalumab plus platinum-etoposide group and 269 in the platinum-etoposide group)

Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. The Lancet. 2019. 394:1929-1939

Study type: Clinical trial
Study name: CASPIAN
Phase: Phase 3
Design: Randomised, controlled, open-label (unblinded) trial at 209 centres in 23 countries; 1:1:1 randomisation to three groups. This paper reports a planned interim analysis comparing durvalumab plus platinum-etoposide with platinum-etoposide alone.
Sample size: 537 patients in the two groups reported in this paper (268 in the durvalumab plus platinum-etoposide group and 269 in the platinum-etoposide group)
Source: The Lancet · 2019
Trial registration: NCT03043872

In plain words

Small-cell lung cancer is often found at an extensive (widespread) stage and is hard to treat. In this study, adding the immunotherapy drug durvalumab to standard chemotherapy (platinum and etoposide) at the start of treatment helped patients live longer on average (13.0 months versus 10.3 months). Serious side effects were about as common in both groups. Talk to your own doctor about whether this treatment is right for you.

Key results

0.73 (95% CI 0.59–0.91)

Hazard ratio (HR) for overall survival

p=0.0047

13.0 months (95% CI 11.5–14.8) vs 10.3 months (9.3–11.2)

Median overall survival

Durvalumab + platinum-etoposide vs platinum-etoposide

34% (26.9–41.0) vs 25% (18.4–31.6)

Patients alive at 18 months

Durvalumab + platinum-etoposide vs platinum-etoposide

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

Dose and schedule cards

Durvalumab + etoposide + platinum (CASPIAN)

Extensive-stage SCLC, no prior chemotherapy; WHO PS 0–1; asymptomatic or treated brain metastases allowedOn the page “Lung cancer” · Small cell lung cancer: first-line

Extensive-stage SCLC, no prior chemotherapy; WHO PS 0–1; asymptomatic or treated brain metastases allowed

Drug	Dose	Route	Schedule
Induction: 4 cycles of 21 days
Durvalumab	1500 mg	IV (60 min)	Day 1 (before chemotherapy)
Carboplatin or cisplatin	AUC 5 or 6, or 75 to 80 mg/m²	IV	Day 1
Etoposide	80 to 100 mg/m²	IV	Days 1, 2 and 3
Maintenance
Durvalumab	1500 mg	IV	Every 4 weeks

Cycle length: Every 21 days (maintenance every 28 days)
Duration: 4 induction cycles, then durvalumab until progression or intolerable toxicity

Source: FDA label for durvalumab (description of the CASPIAN trial); guideline. Body weight less than 30 kg: 20 mg/kg with chemotherapy, then 10 mg/kg every 2 weeks.

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

Platinum/Etop + durvalumab

Extensive-stage small cell lung cancerOn the page “Carboplatin-etoposide with atezolizumab or durvalumab in small cell lung cancer”

Extensive-stage small cell lung cancer

Drug	Dose	Route	Schedule
Phase 1: 4 cycles
Carboplatin (or cisplatin 75 to 80 mg/m²)	AUC 5 to 6	IV	Day 1
Etoposide	80 to 100 mg/m²	IV	Days 1 to 3
Durvalumab	1500 mg	IV	Day 1
Phase 2
Durvalumab	1500 mg	IV	Every 28 days

Cycle length: Chemotherapy every 21 days; maintenance durvalumab every 28 days
Duration: Durvalumab until progression

Doses as in CASPIAN.

Dose source:.

On the page “Carboplatin-etoposide with atezolizumab or durvalumab in small cell lung cancer”

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 + platinum-etoposide

Induction (up to 4 cycles of 21 days): durvalumab 1500 mg IV on day 1 + etoposide 80 to 100 mg/m² IV on days 1 to 3 + investigator's choice of carboplatin AUC 5–6 mg/mL·min or cisplatin 75 to 80 mg/m² IV on day 1 (platinum chosen according to creatinine clearance).

Maintenance: durvalumab 1500 mg IV every 4 weeks until progression or unacceptable toxicity; continuation beyond progression was allowed in clinically stable patients deriving clinical benefit. PCI was not given in this group (268 patients). FDA label for weight <30 kg: 20 mg/kg every 3 weeks with chemotherapy, then 10 mg/kg every 2 weeks.

2Durvalumab + tremelimumab + platinum-etoposide

Induction (up to 4 cycles of 21 days): durvalumab 1500 mg + tremelimumab 75 mg IV on day 1 with the same platinum-etoposide; one additional dose of tremelimumab at week 16. Maintenance: durvalumab 1500 mg every 4 weeks until progression. The results of this group are not reported in this paper.

3Platinum-etoposide (control group)

Up to 6 cycles of platinum-etoposide every 21 days: etoposide 80 to 100 mg/m² IV on days 1 to 3 + investigator's choice of carboplatin AUC 5–6 mg/mL·min or cisplatin 75 to 80 mg/m² IV on day 1 (platinum chosen according to creatinine clearance); then prophylactic cranial irradiation (PCI) at the investigator's discretion (269 patients).

Source of the regimen details: Abstract of the paper, FDA label for Imfinzi (DailyMed, sections 14.2 and 2.2, September 2026 version) and ClinicalTrials.gov NCT03043872 (additional tremelimumab dose at week 16)

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

Adults with untreated extensive-stage small-cell lung cancer (ES-SCLC) suitable for first-line platinum-based chemotherapy, with WHO performance status 0 or 1 and measurable disease (RECIST 1.1). Asymptomatic or treated brain metastases were allowed. Exclusion criteria (FDA label): prior chest radiotherapy, active primary immunodeficiency, autoimmune disorders (including paraneoplastic syndrome) and systemic immunosuppressants within the previous 14 days. Stratified by the planned platinum agent in cycle 1. Patients enrolled between 27 March 2017 and 29 May 2018.

Endpoints

Primary endpoint: overall survival (OS) in the intention-to-treat (ITT) population. Safety was assessed in all patients who received at least one dose of their assigned treatment.

Safety and side effects

Grade 3 or 4 adverse events of any cause occurred in 163 (62%) of 265 treated patients in the durvalumab plus platinum-etoposide group and 166 (62%) of 266 patients in the platinum-etoposide group. Adverse events leading to death occurred in 13 patients (5%) vs 15 patients (6%). According to the FDA label: durvalumab discontinuation due to adverse events 7%; serious adverse events 31% (febrile neutropenia 4.5%, pneumonia 2.3%, anaemia 1.9%, pancytopenia 1.5%, pneumonitis 1.1%). In the control group, 57% of patients received 6 cycles of chemotherapy and 8% received PCI. Safety findings were consistent with the known profiles of all the drugs.

Clinical significance and place in guidelines

According to the abstract, adding durvalumab to platinum-etoposide chemotherapy in first-line treatment of ES-SCLC significantly improved overall survival without a clear increase in grade 3 or 4 adverse events. This finding supports combining immunotherapy with chemotherapy in these patients. The status of drug approvals and formal clinical guideline recommendations should be checked separately and is not covered in the abstract.

Limitations

The trial was open-label (unblinded). The reported results come from a planned interim analysis, and the results of the tremelimumab-containing group are not reported in this paper. The study was funded by AstraZeneca. Further details on limitations are in the full paper.

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.