First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer

L. Horn, Aaron Mansfield, A. Szczȩsna, L. Havel, M. Krzakowski, M. J. Hochmair, F. Huemer, G. Losonczy, M. L. Johnson, M. Nishio, M. Reck, T. Mok, S. Lam, D. S. Shames, J. Liu, B. Ding, A. Lopez-Chavez, F. Kabbinavar, W. Lin, A. SandlerS. V. Liu

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy. METHODS: We conducted this double-blind, placebo-controlled, phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive-stage small-cell lung cancer who had not previously received treatment. Patients were randomly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21-day cycles (induction phase), followed by a maintenance phase during which they received either atezolizumab or placebo (according to the previous random assignment) until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical benefit. The two primary end points were investigator-assessed progression-free survival and overall survival in the intentionto- treat population. RESULTS: A total of 201 patients were randomly assigned to the atezolizumab group, and 202 patients to the placebo group. At a median follow-up of 13.9 months, the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio for death, 0.70; 95% confidence interval [CI], 0.54 to 0.91; P = 0.007). The median progression-free survival was 5.2 months and 4.3 months, respectively (hazard ratio for disease progression or death, 0.77; 95% CI, 0.62 to 0.96; P = 0.02). The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents, with no new findings observed. CONCLUSIONS: The addition of atezolizumab to chemotherapy in the first-line treatment of extensive- stage small-cell lung cancer resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.

Original languageEnglish (US)
Pages (from-to)2220-2229
Number of pages10
JournalNew England Journal of Medicine
Volume379
Issue number23
DOIs
StatePublished - Dec 6 2018

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Small Cell Lung Carcinoma
Drug Therapy
Placebos
Carboplatin
Etoposide
Disease-Free Survival
Survival
Disease Progression
Confidence Intervals
Safety
Poisons
MPDL3280A
Immunity
Therapeutics
Maintenance
Research Personnel
Ligands
T-Lymphocytes
Population
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

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Horn, L., Mansfield, A., Szczȩsna, A., Havel, L., Krzakowski, M., Hochmair, M. J., ... Liu, S. V. (2018). First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. New England Journal of Medicine, 379(23), 2220-2229. https://doi.org/10.1056/NEJMoa1809064

First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. / Horn, L.; Mansfield, Aaron; Szczȩsna, A.; Havel, L.; Krzakowski, M.; Hochmair, M. J.; Huemer, F.; Losonczy, G.; Johnson, M. L.; Nishio, M.; Reck, M.; Mok, T.; Lam, S.; Shames, D. S.; Liu, J.; Ding, B.; Lopez-Chavez, A.; Kabbinavar, F.; Lin, W.; Sandler, A.; Liu, S. V.

In: New England Journal of Medicine, Vol. 379, No. 23, 06.12.2018, p. 2220-2229.

Research output: Contribution to journalArticle

Horn, L, Mansfield, A, Szczȩsna, A, Havel, L, Krzakowski, M, Hochmair, MJ, Huemer, F, Losonczy, G, Johnson, ML, Nishio, M, Reck, M, Mok, T, Lam, S, Shames, DS, Liu, J, Ding, B, Lopez-Chavez, A, Kabbinavar, F, Lin, W, Sandler, A & Liu, SV 2018, 'First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer', New England Journal of Medicine, vol. 379, no. 23, pp. 2220-2229. https://doi.org/10.1056/NEJMoa1809064
Horn, L. ; Mansfield, Aaron ; Szczȩsna, A. ; Havel, L. ; Krzakowski, M. ; Hochmair, M. J. ; Huemer, F. ; Losonczy, G. ; Johnson, M. L. ; Nishio, M. ; Reck, M. ; Mok, T. ; Lam, S. ; Shames, D. S. ; Liu, J. ; Ding, B. ; Lopez-Chavez, A. ; Kabbinavar, F. ; Lin, W. ; Sandler, A. ; Liu, S. V. / First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. In: New England Journal of Medicine. 2018 ; Vol. 379, No. 23. pp. 2220-2229.
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abstract = "BACKGROUND: Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy. METHODS: We conducted this double-blind, placebo-controlled, phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive-stage small-cell lung cancer who had not previously received treatment. Patients were randomly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21-day cycles (induction phase), followed by a maintenance phase during which they received either atezolizumab or placebo (according to the previous random assignment) until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical benefit. The two primary end points were investigator-assessed progression-free survival and overall survival in the intentionto- treat population. RESULTS: A total of 201 patients were randomly assigned to the atezolizumab group, and 202 patients to the placebo group. At a median follow-up of 13.9 months, the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio for death, 0.70; 95{\%} confidence interval [CI], 0.54 to 0.91; P = 0.007). The median progression-free survival was 5.2 months and 4.3 months, respectively (hazard ratio for disease progression or death, 0.77; 95{\%} CI, 0.62 to 0.96; P = 0.02). The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents, with no new findings observed. CONCLUSIONS: The addition of atezolizumab to chemotherapy in the first-line treatment of extensive- stage small-cell lung cancer resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.",
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T1 - First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer

AU - Horn, L.

AU - Mansfield, Aaron

AU - Szczȩsna, A.

AU - Havel, L.

AU - Krzakowski, M.

AU - Hochmair, M. J.

AU - Huemer, F.

AU - Losonczy, G.

AU - Johnson, M. L.

AU - Nishio, M.

AU - Reck, M.

AU - Mok, T.

AU - Lam, S.

AU - Shames, D. S.

AU - Liu, J.

AU - Ding, B.

AU - Lopez-Chavez, A.

AU - Kabbinavar, F.

AU - Lin, W.

AU - Sandler, A.

AU - Liu, S. V.

PY - 2018/12/6

Y1 - 2018/12/6

N2 - BACKGROUND: Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy. METHODS: We conducted this double-blind, placebo-controlled, phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive-stage small-cell lung cancer who had not previously received treatment. Patients were randomly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21-day cycles (induction phase), followed by a maintenance phase during which they received either atezolizumab or placebo (according to the previous random assignment) until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical benefit. The two primary end points were investigator-assessed progression-free survival and overall survival in the intentionto- treat population. RESULTS: A total of 201 patients were randomly assigned to the atezolizumab group, and 202 patients to the placebo group. At a median follow-up of 13.9 months, the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio for death, 0.70; 95% confidence interval [CI], 0.54 to 0.91; P = 0.007). The median progression-free survival was 5.2 months and 4.3 months, respectively (hazard ratio for disease progression or death, 0.77; 95% CI, 0.62 to 0.96; P = 0.02). The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents, with no new findings observed. CONCLUSIONS: The addition of atezolizumab to chemotherapy in the first-line treatment of extensive- stage small-cell lung cancer resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.

AB - BACKGROUND: Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy. METHODS: We conducted this double-blind, placebo-controlled, phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive-stage small-cell lung cancer who had not previously received treatment. Patients were randomly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21-day cycles (induction phase), followed by a maintenance phase during which they received either atezolizumab or placebo (according to the previous random assignment) until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical benefit. The two primary end points were investigator-assessed progression-free survival and overall survival in the intentionto- treat population. RESULTS: A total of 201 patients were randomly assigned to the atezolizumab group, and 202 patients to the placebo group. At a median follow-up of 13.9 months, the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio for death, 0.70; 95% confidence interval [CI], 0.54 to 0.91; P = 0.007). The median progression-free survival was 5.2 months and 4.3 months, respectively (hazard ratio for disease progression or death, 0.77; 95% CI, 0.62 to 0.96; P = 0.02). The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents, with no new findings observed. CONCLUSIONS: The addition of atezolizumab to chemotherapy in the first-line treatment of extensive- stage small-cell lung cancer resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.

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