Enriqueta Felip1, Nasser Altorki2, Caicun Zhou3, Tibor Csőszi4, Ihor Vynnychenko5, Oleksandr Goloborodko6, Alexander Luft7, Andrey Akopov8, Alex Martinez-Marti9, Hirotsugu Kenmotsu10, Yuh-Min Chen11, Antonio Chella12, Shunichi Sugawara13, David Voong14, Fan Wu15, Jing Yi14, Yu Deng14, Mark McCleland14, Elizabeth Bennett14, Barbara Gitlitz14, Heather Wakelee16. 1. Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain. Electronic address: efelip@vhio.net. 2. Division of Thoracic Surgery, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA. 3. Department of Oncology, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China. 4. Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelőintézet, Szolnok, Hungary. 5. Regional Municipal Institution Sumy Regional Clinical Oncology Dispensary, Sumy State University, Sumy, Ukraine. 6. MI Zaporizhzhia Regional Clinical Oncological Dispensary Zaporizhzhia SMU Ch of Oncology, Zaporizhzhya, Ukraine. 7. Department of Thoracic Surgery, Leningrad Regional Clinical Hospital, Saint Petersburg, Russia. 8. Research Institute of Pulmonology, Pavlov State Medical University, Saint Petersburg, Russia. 9. Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain. 10. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 11. Department of Chest Medicine, Taipei Veterans General Hospital and National Yang Ming Chiao Tung University, Taipei, Taiwan. 12. Pneumology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. 13. Department of Pulmonary Medicine, Sendai Kousei Hospital, Miyagi, Japan. 14. Genentech, South San Francisco, CA, USA. 15. Roche (China) Holding, Shanghai, China. 16. Department of Medicine, Division of Oncology, Stanford University School of Medicine and Stanford Cancer Institute, Stanford, CA, USA.
Abstract
BACKGROUND: Novel adjuvant strategies are needed to optimise outcomes after complete surgical resection in patients with early-stage non-small-cell lung cancer (NSCLC). We aimed to evaluate adjuvant atezolizumab versus best supportive care after adjuvant platinum-based chemotherapy in these patients. METHODS: IMpower010 was a randomised, multicentre, open-label, phase 3 study done at 227 sites in 22 countries and regions. Eligible patients were 18 years or older with completely resected stage IB (tumours ≥4 cm) to IIIA NSCLC per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system (7th edition). Patients were randomly assigned (1:1) by a permuted-block method (block size of four) to receive adjuvant atezolizumab (1200 mg every 21 days; for 16 cycles or 1 year) or best supportive care (observation and regular scans for disease recurrence) after adjuvant platinum-based chemotherapy (one to four cycles). The primary endpoint, investigator-assessed disease-free survival, was tested hierarchically first in the stage II-IIIA population subgroup whose tumours expressed PD-L1 on 1% or more of tumour cells (SP263), then all patients in 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 and received 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 complete resection. 1269 received adjuvant chemotherapy, of whom 1005 patients were eligible for randomisation to atezolizumab (n=507) or best supportive care (n=498); 495 in each 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 survival compared with best supportive care in patients in the stage II-IIIA population whose tumours 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 patients and grade 5 events in four patients (1%). INTERPRETATION: IMpower010 showed a disease-free survival benefit with atezolizumab versus best supportive care after adjuvant chemotherapy in patients with resected stage II-IIIA NSCLC, with pronounced benefit in the subgroup whose tumours expressed PD-L1 on 1% or more of tumour cells, and no new safety signals. Atezolizumab after adjuvant chemotherapy offers a promising treatment option for patients with resected early-stage NSCLC. FUNDING: F Hoffmann-La Roche and Genentech.
BACKGROUND: Novel adjuvant strategies are needed to optimise outcomes after complete surgical resection in patients with early-stage non-small-cell lung cancer (NSCLC). We aimed to evaluate adjuvant atezolizumab versus best supportive care after adjuvant platinum-based chemotherapy in these patients. METHODS: IMpower010 was a randomised, multicentre, open-label, phase 3 study done at 227 sites in 22 countries and regions. Eligible patients were 18 years or older with completely resected stage IB (tumours ≥4 cm) to IIIA NSCLC per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system (7th edition). Patients were randomly assigned (1:1) by a permuted-block method (block size of four) to receive adjuvant atezolizumab (1200 mg every 21 days; for 16 cycles or 1 year) or best supportive care (observation and regular scans for disease recurrence) after adjuvant platinum-based chemotherapy (one to four cycles). The primary endpoint, investigator-assessed disease-free survival, was tested hierarchically first in the stage II-IIIA population subgroup whose tumours expressed PD-L1 on 1% or more of tumour cells (SP263), then all patients in 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 and received 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 complete resection. 1269 received adjuvant chemotherapy, of whom 1005 patients were eligible for randomisation to atezolizumab (n=507) or best supportive care (n=498); 495 in each 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 survival compared with best supportive care in patients in the stage II-IIIA population whose tumours 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 patients and grade 5 events in four patients (1%). INTERPRETATION: IMpower010 showed a disease-free survival benefit with atezolizumab versus best supportive care after adjuvant chemotherapy in patients with resected stage II-IIIA NSCLC, with pronounced benefit in the subgroup whose tumours expressed PD-L1 on 1% or more of tumour cells, and no new safety signals. Atezolizumab after adjuvant chemotherapy offers a promising treatment option for patients with resected early-stage NSCLC. FUNDING: F Hoffmann-La Roche and Genentech.
Authors: Daan C L Vessies; Milou M F Schuurbiers; Vincent van der Noort; Irene Schouten; Theodora C Linders; Mirthe Lanfermeijer; Kalpana L Ramkisoensing; Koen J Hartemink; Kim Monkhorst; Michel M van den Heuvel; Daan van den Broek Journal: Mol Oncol Date: 2022-06-27 Impact factor: 7.449