Robert Jotte1, Federico Cappuzzo2, Ihor Vynnychenko3, Daniil Stroyakovskiy4, Delvys Rodríguez-Abreu5, Maen Hussein6, Ross Soo7, Henry J Conter8, Toshiyuki Kozuki9, Kuan-Chieh Huang10, Vilma Graupner11, Shawn W Sun10, Tien Hoang10, Helen Jessop12, Mark McCleland10, Marcus Ballinger10, Alan Sandler10, Mark A Socinski13. 1. Department of Medical Oncology, Rocky Mountain Cancer Centers, Denver, Colorado; US Oncology, Houston, Texas. Electronic address: robert.jotte@usoncology.com. 2. Department of Oncology and Hematology, Azienda Unità Sanitaria Locale della Romagna, Ravenna, Italy. 3. Department of Oncology and Radiology, Sumy State University, Sumy, Ukraine. 4. Chemotherapeutic Department, Moscow City Oncology Hospital, Moscow Healthcare Department, Moscow, Russia. 5. Department of Medical Oncology, Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain. 6. Department of Cancer Research, Florida Cancer Specialists, Lady Lake, Florida; Sarah Cannon Research Institute, Nashville, Tennessee. 7. Department of Hematology-Oncology, National University Hospital, Singapore. 8. Department of Medicine, William Osler Health System, Brampton, Ontario, Canada. 9. National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 10. Product Development, Oncology Genentech, Inc., South San Francisco, California. 11. Product Development, Oncology F. Hoffmann-La Roche, Ltd., Basel, Switzerland. 12. Department of Clinical Safety, Roche Products Ltd., Welwyn Garden City, United Kingdom. 13. Department of Thoracic Oncology, AdventHealth Cancer Institute, Orlando, Florida.
Abstract
INTRODUCTION: Cytotoxic agents have immunomodulatory effects, providing a rationale for combining atezolizumab (anti-programmed death-ligand 1 [anti-PD-L1]) with chemotherapy. The randomized phase III IMpower131 study (NCT02367794) evaluated atezolizumab with platinum-based chemotherapy in stage IV squamous NSCLC. METHODS: A total of 1021 patients were randomized 1:1:1 to receive atezolizumab+carboplatin+paclitaxel (A+CP) (n = 338), atezolizumab+carboplatin+nab-paclitaxel (A+CnP) (n = 343), or carboplatin+nab-paclitaxel (CnP) (n = 340) for four or six 21-day cycles; patients randomized to the A+CP or A+CnP arms received atezolizumab maintenance therapy until progressive disease or loss of clinical benefit. The coprimary end points were investigator-assessed progression-free survival (PFS) and overall survival (OS) in the intention-to-treat (ITT) population. The secondary end points included PFS and OS in PD-L1 subgroups and safety. The primary PFS (January 22, 2018) and final OS (October 3, 2018) for A+CnP versus CnP are reported. RESULTS:PFS improvement with A+CnP versus CnP was seen in the ITT population (median, 6.3 versus 5.6 mo; hazard ratio [HR] = 0.71, 95% confidence interval [CI]: 0.60-0.85; p = 0.0001). Median OS in the ITT population was 14.2 and 13.5 months in the A+CnP and CnP arms (HR = 0.88, 95% CI: 0.73-1.05; p = 0.16), not reaching statistical significance. OS improvement with A+CnP versus CnP was observed in the PD-L1-high subgroup (HR = 0.48, 95% CI: 0.29-0.81), despite not being formally tested. Treatment-related grade 3 and 4 adverse events and serious adverse events occurred in 68.0% and 47.9% (A+CnP) and 57.5% and 28.7% (CnP) of patients, respectively. CONCLUSIONS: Adding atezolizumab to platinum-based chemotherapy significantly improved PFS in patients with first-line squamous NSCLC; OS was similar between the arms.
RCT Entities:
INTRODUCTION: Cytotoxic agents have immunomodulatory effects, providing a rationale for combining atezolizumab (anti-programmed death-ligand 1 [anti-PD-L1]) with chemotherapy. The randomized phase III IMpower131 study (NCT02367794) evaluated atezolizumab with platinum-based chemotherapy in stage IV squamous NSCLC. METHODS: A total of 1021 patients were randomized 1:1:1 to receive atezolizumab+carboplatin+paclitaxel (A+CP) (n = 338), atezolizumab+carboplatin+nab-paclitaxel (A+CnP) (n = 343), or carboplatin+nab-paclitaxel (CnP) (n = 340) for four or six 21-day cycles; patients randomized to the A+CP or A+CnP arms received atezolizumab maintenance therapy until progressive disease or loss of clinical benefit. The coprimary end points were investigator-assessed progression-free survival (PFS) and overall survival (OS) in the intention-to-treat (ITT) population. The secondary end points included PFS and OS in PD-L1 subgroups and safety. The primary PFS (January 22, 2018) and final OS (October 3, 2018) for A+CnP versus CnP are reported. RESULTS: PFS improvement with A+CnP versus CnP was seen in the ITT population (median, 6.3 versus 5.6 mo; hazard ratio [HR] = 0.71, 95% confidence interval [CI]: 0.60-0.85; p = 0.0001). Median OS in the ITT population was 14.2 and 13.5 months in the A+CnP and CnP arms (HR = 0.88, 95% CI: 0.73-1.05; p = 0.16), not reaching statistical significance. OS improvement with A+CnP versus CnP was observed in the PD-L1-high subgroup (HR = 0.48, 95% CI: 0.29-0.81), despite not being formally tested. Treatment-related grade 3 and 4 adverse events and serious adverse events occurred in 68.0% and 47.9% (A+CnP) and 57.5% and 28.7% (CnP) of patients, respectively. CONCLUSIONS: Adding atezolizumab to platinum-based chemotherapy significantly improved PFS in patients with first-line squamous NSCLC; OS was similar between the arms.
Authors: Deborah Blythe Doroshow; Sheena Bhalla; Mary Beth Beasley; Lynette M Sholl; Keith M Kerr; Sacha Gnjatic; Ignacio I Wistuba; David L Rimm; Ming Sound Tsao; Fred R Hirsch Journal: Nat Rev Clin Oncol Date: 2021-02-12 Impact factor: 66.675
Authors: Zia Khan; Christian Hammer; Jonathan Carroll; Flavia Di Nucci; Sergio Ley Acosta; Vidya Maiya; Tushar Bhangale; Julie Hunkapiller; Ira Mellman; Matthew L Albert; Mark I McCarthy; G Scott Chandler Journal: Nat Commun Date: 2021-06-07 Impact factor: 14.919