Stephen V Liu1, D Ross Camidge2, Scott N Gettinger3, Giuseppe Giaccone4, Rebecca S Heist5, F Stephen Hodi6, Neal E Ready7, Wei Zhang8, Jeffrey Wallin9, Roel Funke10, Daniel Waterkamp11, Paul Foster12, Koho Iizuka13, John Powderly14. 1. Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Rd NW, Washington, DC, USA. Electronic address: Stephen.V.Liu@gunet.georgetown.edu. 2. University of Colorado Denver, 13001 E 17th Place, Aurora, CO, USA. Electronic address: ross.camidge@ucdenver.edu. 3. Yale Cancer Center, 333 Cedar St, New Haven, CT, USA. Electronic address: scott.gettinger@yale.edu. 4. Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Rd NW, Washington, DC, USA. Electronic address: gg496@georgetown.edu. 5. Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA. Electronic address: rheist@partners.org. 6. Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. Electronic address: Stephen_Hodi@dfci.harvard.edu. 7. Duke University Medical Center, 10 Duke Medicine Circle, Durham, NC 27710, USA. Electronic address: neal.ready@duke.edu. 8. Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: zhang.wei_zhanw107@gene.com. 9. Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: jwallin@seagen.com. 10. Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: funke.roel@gene.com. 11. Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: waterkamp.daniel@gene.com. 12. Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: foster.paul@gene.com. 13. Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: iizuka.koho@gene.com. 14. Carolina BioOncology Institute, 9801 Kincey Ave, Huntersville, NC 28078, USA. Electronic address: jpowderly@carolinabiooncology.org.
Abstract
BACKGROUND: Before the availability of immunotherapy, chemotherapy was standard first-line therapy for non-small-cell lung cancer (NSCLC) lacking actionable gene alterations. Preclinical evidence suggests chemotherapy is immunomodulatory, supporting chemotherapy/immunotherapy combinations. Atezolizumab, anti-programmed death ligand-1 (PD-L1) antibody, blocks programmed cell death protein-1 and B7.1 interaction with PD-L1. GP28328 (NCT01633970) assessed atezolizumab with chemotherapy in multiple tumours; we report results for advanced, treatment-naïve NSCLC. METHODS: Patients received atezolizumab plus carboplatin with paclitaxel (Arm C: atezo/cb/pac), pemetrexed (Arm D: atezo/cb/pem, maintenance pemetrexed permitted), or nab-paclitaxel (Arm E: atezo/cb/nab-pac), four-six cycles, then atezolizumab maintenance. Primary end-point was safety; secondary end-points were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS:Seventy-six NSCLC patients were enrolled (n = 25, 25 and 26 for Arms C, D and E, respectively). Common treatment-related grade III/IV adverse events were neutropenia (36% atezo/cb/pac, 36% atezo/cb/pem, 42% atezo/cb/nab-pac) and anaemia (16% atezo/cb/pac, 16% atezo/cb/pem, 31% atezo/cb/nab-pac). Confirmed ORRs were 36% atezo/cb/pac, 68% atezo/cb/pem (one complete response [CR]) and 46% atezo/cb/nab-pac (four CRs). Median PFS was 7.1 months, (95% confidence interval [CI]: 4.2-8.3), 8.4 months (95% CI: 4.7-11) and 5.7 months (95% CI: 4.4-14.8), respectively. Median OS was 12.9 months (95% CI: 8.8-21.3), 18.9 months (95% CI: 9.9-27.4) and 17.0 months (95% CI: 12.7-not evaluable), respectively. CONCLUSION:Atezolizumab with chemotherapy was well tolerated with encouraging efficacy, though the analysis was limited by small numbers. NSCLC chemotherapy combination studies are ongoing. CLINICALTRIALS. GOV IDENTIFIER: NCT01633970.
RCT Entities:
BACKGROUND: Before the availability of immunotherapy, chemotherapy was standard first-line therapy for non-small-cell lung cancer (NSCLC) lacking actionable gene alterations. Preclinical evidence suggests chemotherapy is immunomodulatory, supporting chemotherapy/immunotherapy combinations. Atezolizumab, anti-programmed death ligand-1 (PD-L1) antibody, blocks programmed cell death protein-1 and B7.1 interaction with PD-L1. GP28328 (NCT01633970) assessed atezolizumab with chemotherapy in multiple tumours; we report results for advanced, treatment-naïve NSCLC. METHODS:Patients received atezolizumab plus carboplatin with paclitaxel (Arm C: atezo/cb/pac), pemetrexed (Arm D: atezo/cb/pem, maintenance pemetrexed permitted), or nab-paclitaxel (Arm E: atezo/cb/nab-pac), four-six cycles, then atezolizumab maintenance. Primary end-point was safety; secondary end-points were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: Seventy-six NSCLCpatients were enrolled (n = 25, 25 and 26 for Arms C, D and E, respectively). Common treatment-related grade III/IV adverse events were neutropenia (36% atezo/cb/pac, 36% atezo/cb/pem, 42% atezo/cb/nab-pac) and anaemia (16% atezo/cb/pac, 16% atezo/cb/pem, 31% atezo/cb/nab-pac). Confirmed ORRs were 36% atezo/cb/pac, 68% atezo/cb/pem (one complete response [CR]) and 46% atezo/cb/nab-pac (four CRs). Median PFS was 7.1 months, (95% confidence interval [CI]: 4.2-8.3), 8.4 months (95% CI: 4.7-11) and 5.7 months (95% CI: 4.4-14.8), respectively. Median OS was 12.9 months (95% CI: 8.8-21.3), 18.9 months (95% CI: 9.9-27.4) and 17.0 months (95% CI: 12.7-not evaluable), respectively. CONCLUSION:Atezolizumab with chemotherapy was well tolerated with encouraging efficacy, though the analysis was limited by small numbers. NSCLC chemotherapy combination studies are ongoing. CLINICALTRIALS. GOV IDENTIFIER: NCT01633970.
Authors: Sylvia Adams; Jennifer R Diamond; Erika Hamilton; Paula R Pohlmann; Sara M Tolaney; Ching-Wei Chang; Wei Zhang; Koho Iizuka; Paul G Foster; Luciana Molinero; Roel Funke; John Powderly Journal: JAMA Oncol Date: 2019-03-01 Impact factor: 31.777