Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial
Mené sur 1 280 patients atteints d'un cancer du poumon non à petites cellules de stade IB-IIIA ayant été réséqué, cet essai de phase III compare l'efficacité, du point de vue de la survie sans maladie, et la toxicité de l'atézolizumab en traitement adjuvant et des "meilleurs soins de support", après une chimiothérapie adjuvante à base de sels de platine
Background : Novel adjuvant strategies are needed to optimise outcomes after complete surgicalresection in patients with early-stage non-small-cell lung cancer (NSCLC). We aimedto evaluate adjuvant atezolizumab versus best supportive care after adjuvant platinum-basedchemotherapy in these patients. Methods : IMpower010 was a randomised, multicentre, open-label, phase 3 study done at 227 sitesin 22 countries and regions. Eligible patients were 18 years or older with completelyresected stage IB (tumours ≥4 cm) to IIIA NSCLC per the Union Internationale Contrele Cancer and American Joint Committee on Cancer staging system (7th edition). Patientswere randomly assigned (1:1) by a permuted-block method (block size of four) to receiveadjuvant atezolizumab (1200 mg every 21 days; for 16 cycles or 1 year) or best supportivecare (observation and regular scans for disease recurrence) after adjuvant platinum-basedchemotherapy (one to four cycles). The primary endpoint, investigator-assessed disease-free survival, was tested hierarchically first in the stage II–IIIA population subgroupwhose tumours expressed PD-L1 on 1% or more of tumour cells (SP263), then all patientsin the stage II–IIIA population, and finally the intention-to-treat (ITT) population(stage IB–IIIA). Safety was evaluated in all patients who were randomly assigned andreceived atezolizumab or best supportive care. IMpower010 is registered with ClinicalTrials.gov, NCT02486718 (active, not recruiting). Findings : Between Oct 7, 2015, and Sept 19, 2018, 1280 patients were enrolled after completeresection. 1269 received adjuvant chemotherapy, of whom 1005 patients were eligiblefor randomisation to atezolizumab (n=507) or best supportive care (n=498); 495 ineach group received treatment. After a median follow-up of 32·2 months (IQR 27·4–38·3)in the stage II–IIIA population, atezolizumab treatment improved disease-free survivalcompared with best supportive care in patients in the stage II–IIIA population whosetumours expressed PD-L1 on 1% or more of tumour cells (HR 0·66; 95% CI 0·50–0·88;p=0·0039) and in all patients in the stage II–IIIA population (0·79; 0·64–0·96; p=0·020).In the ITT population, HR for disease-free survival was 0·81 (0·67–0·99; p=0·040).Atezolizumab-related grade 3 and 4 adverse events occurred in 53 (11%) of 495 patientsand grade 5 events in four patients (1%). Interpretation : IMpower010 showed a disease-free survival benefit with atezolizumab versus best supportivecare after adjuvant chemotherapy in patients with resected stage II–IIIA NSCLC, withpronounced benefit in the subgroup whose tumours expressed PD-L1 on 1% or more oftumour cells, and no new safety signals. Atezolizumab after adjuvant chemotherapyoffers a promising treatment option for patients with resected early-stage NSCLC.
The Lancet 2021