Updated Efficacy Analysis Including Secondary Population Results for OAK: A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non–Small Cell Lung Cancer

Louis Fehrenbacher, Joachim von Pawel, Keunchil Park, Achim Rittmeyer, David R Gandara, Santiago Ponce Aix, Ji Youn Han, Shirish M. Gadgeel, Toyoaki Hida, Diego L. Cortinovis, Manuel Cobo, Dariusz M. Kowalski, Filippo De Marinis, Mayank Gandhi, Bradford Danner, Christina Matheny, Marcin Kowanetz, Pei He, Federico Felizzi, Hina PatelAlan Sandler, Marcus Ballinger, Fabrice Barlesi

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Abstract

Introduction: The efficacy and safety of atezolizumab versus the efficacy and safety of docetaxel as second- or third-line treatment in patients with advanced NSCLC in the primary (n = 850) and secondary (n = 1225) efficacy populations of the randomized phase III OAK study (respectively referred to as the intention-to-treat [ITT] 850 [ITT850] and ITT1225) at an updated data cutoff were assessed. Methods: Patients received atezolizumab, 1200 mg, or docetaxel, 75 mg/m2, intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively. The primary end point was overall survival (OS) in the ITT population and programmed death-ligand 1–expressing subgroup. A sensitivity analysis was conducted to evaluate the impact of subsequent immunotherapy use in the docetaxel arm on the observed survival benefit with atezolizumab. Results: Atezolizumab demonstrated an OS benefit versus docetaxel in the updated ITT850 (hazard ratio [HR] = 0.75, 95% confidence interval: 0.64–0.89, p = 0.0006) and the ITT1225 (HR = 0.80, 95% confidence interval: 0.70–0.92, p = 0.0012) after minimum follow-up times of 26 and 21 months, respectively. Improved survival with atezolizumab was observed across programmed death-ligand 1 and histological subgroups. In the immunotherapy sensitivity analysis, the relative OS benefit with atezolizumab was slightly greater in the ITT850 (HR = 0.69) and ITT1225 (HR = 0.74) than the conventional OS estimate. Fewer patients receiving atezolizumab experienced grade 3 or 4 treatment-related adverse events (14.9%) than did patients receiving docetaxel (42.4%); no grade 5 adverse events related to atezolizumab were observed. Conclusions: The results of the updated ITT850 and initial ITT1225 analyses were consistent with those of the primary efficacy analysis demonstrating survival benefit with atezolizumab versus with docetaxel. Atezolizumab continued to demonstrate a favorable safety profile after longer treatment exposure and follow-up.

Original languageEnglish (US)
Pages (from-to)1156-1170
Number of pages15
JournalJournal of Thoracic Oncology
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2018

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docetaxel
Non-Small Cell Lung Carcinoma
Population
Survival
Safety
Immunotherapy
MPDL3280A
Confidence Intervals
Ligands

Keywords

  • Atezolizumab
  • Cancer immunotherapy
  • Checkpoint inhibitor
  • Non–small cell lung cancer
  • PD-L1

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Updated Efficacy Analysis Including Secondary Population Results for OAK : A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non–Small Cell Lung Cancer. / Fehrenbacher, Louis; von Pawel, Joachim; Park, Keunchil; Rittmeyer, Achim; Gandara, David R; Ponce Aix, Santiago; Han, Ji Youn; Gadgeel, Shirish M.; Hida, Toyoaki; Cortinovis, Diego L.; Cobo, Manuel; Kowalski, Dariusz M.; De Marinis, Filippo; Gandhi, Mayank; Danner, Bradford; Matheny, Christina; Kowanetz, Marcin; He, Pei; Felizzi, Federico; Patel, Hina; Sandler, Alan; Ballinger, Marcus; Barlesi, Fabrice.

In: Journal of Thoracic Oncology, Vol. 13, No. 8, 01.08.2018, p. 1156-1170.

Research output: Contribution to journalArticle

Fehrenbacher, L, von Pawel, J, Park, K, Rittmeyer, A, Gandara, DR, Ponce Aix, S, Han, JY, Gadgeel, SM, Hida, T, Cortinovis, DL, Cobo, M, Kowalski, DM, De Marinis, F, Gandhi, M, Danner, B, Matheny, C, Kowanetz, M, He, P, Felizzi, F, Patel, H, Sandler, A, Ballinger, M & Barlesi, F 2018, 'Updated Efficacy Analysis Including Secondary Population Results for OAK: A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non–Small Cell Lung Cancer', Journal of Thoracic Oncology, vol. 13, no. 8, pp. 1156-1170. https://doi.org/10.1016/j.jtho.2018.04.039
Fehrenbacher, Louis ; von Pawel, Joachim ; Park, Keunchil ; Rittmeyer, Achim ; Gandara, David R ; Ponce Aix, Santiago ; Han, Ji Youn ; Gadgeel, Shirish M. ; Hida, Toyoaki ; Cortinovis, Diego L. ; Cobo, Manuel ; Kowalski, Dariusz M. ; De Marinis, Filippo ; Gandhi, Mayank ; Danner, Bradford ; Matheny, Christina ; Kowanetz, Marcin ; He, Pei ; Felizzi, Federico ; Patel, Hina ; Sandler, Alan ; Ballinger, Marcus ; Barlesi, Fabrice. / Updated Efficacy Analysis Including Secondary Population Results for OAK : A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non–Small Cell Lung Cancer. In: Journal of Thoracic Oncology. 2018 ; Vol. 13, No. 8. pp. 1156-1170.
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abstract = "Introduction: The efficacy and safety of atezolizumab versus the efficacy and safety of docetaxel as second- or third-line treatment in patients with advanced NSCLC in the primary (n = 850) and secondary (n = 1225) efficacy populations of the randomized phase III OAK study (respectively referred to as the intention-to-treat [ITT] 850 [ITT850] and ITT1225) at an updated data cutoff were assessed. Methods: Patients received atezolizumab, 1200 mg, or docetaxel, 75 mg/m2, intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively. The primary end point was overall survival (OS) in the ITT population and programmed death-ligand 1–expressing subgroup. A sensitivity analysis was conducted to evaluate the impact of subsequent immunotherapy use in the docetaxel arm on the observed survival benefit with atezolizumab. Results: Atezolizumab demonstrated an OS benefit versus docetaxel in the updated ITT850 (hazard ratio [HR] = 0.75, 95{\%} confidence interval: 0.64–0.89, p = 0.0006) and the ITT1225 (HR = 0.80, 95{\%} confidence interval: 0.70–0.92, p = 0.0012) after minimum follow-up times of 26 and 21 months, respectively. Improved survival with atezolizumab was observed across programmed death-ligand 1 and histological subgroups. In the immunotherapy sensitivity analysis, the relative OS benefit with atezolizumab was slightly greater in the ITT850 (HR = 0.69) and ITT1225 (HR = 0.74) than the conventional OS estimate. Fewer patients receiving atezolizumab experienced grade 3 or 4 treatment-related adverse events (14.9{\%}) than did patients receiving docetaxel (42.4{\%}); no grade 5 adverse events related to atezolizumab were observed. Conclusions: The results of the updated ITT850 and initial ITT1225 analyses were consistent with those of the primary efficacy analysis demonstrating survival benefit with atezolizumab versus with docetaxel. Atezolizumab continued to demonstrate a favorable safety profile after longer treatment exposure and follow-up.",
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TY - JOUR

T1 - Updated Efficacy Analysis Including Secondary Population Results for OAK

T2 - A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non–Small Cell Lung Cancer

AU - Fehrenbacher, Louis

AU - von Pawel, Joachim

AU - Park, Keunchil

AU - Rittmeyer, Achim

AU - Gandara, David R

AU - Ponce Aix, Santiago

AU - Han, Ji Youn

AU - Gadgeel, Shirish M.

AU - Hida, Toyoaki

AU - Cortinovis, Diego L.

AU - Cobo, Manuel

AU - Kowalski, Dariusz M.

AU - De Marinis, Filippo

AU - Gandhi, Mayank

AU - Danner, Bradford

AU - Matheny, Christina

AU - Kowanetz, Marcin

AU - He, Pei

AU - Felizzi, Federico

AU - Patel, Hina

AU - Sandler, Alan

AU - Ballinger, Marcus

AU - Barlesi, Fabrice

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Introduction: The efficacy and safety of atezolizumab versus the efficacy and safety of docetaxel as second- or third-line treatment in patients with advanced NSCLC in the primary (n = 850) and secondary (n = 1225) efficacy populations of the randomized phase III OAK study (respectively referred to as the intention-to-treat [ITT] 850 [ITT850] and ITT1225) at an updated data cutoff were assessed. Methods: Patients received atezolizumab, 1200 mg, or docetaxel, 75 mg/m2, intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively. The primary end point was overall survival (OS) in the ITT population and programmed death-ligand 1–expressing subgroup. A sensitivity analysis was conducted to evaluate the impact of subsequent immunotherapy use in the docetaxel arm on the observed survival benefit with atezolizumab. Results: Atezolizumab demonstrated an OS benefit versus docetaxel in the updated ITT850 (hazard ratio [HR] = 0.75, 95% confidence interval: 0.64–0.89, p = 0.0006) and the ITT1225 (HR = 0.80, 95% confidence interval: 0.70–0.92, p = 0.0012) after minimum follow-up times of 26 and 21 months, respectively. Improved survival with atezolizumab was observed across programmed death-ligand 1 and histological subgroups. In the immunotherapy sensitivity analysis, the relative OS benefit with atezolizumab was slightly greater in the ITT850 (HR = 0.69) and ITT1225 (HR = 0.74) than the conventional OS estimate. Fewer patients receiving atezolizumab experienced grade 3 or 4 treatment-related adverse events (14.9%) than did patients receiving docetaxel (42.4%); no grade 5 adverse events related to atezolizumab were observed. Conclusions: The results of the updated ITT850 and initial ITT1225 analyses were consistent with those of the primary efficacy analysis demonstrating survival benefit with atezolizumab versus with docetaxel. Atezolizumab continued to demonstrate a favorable safety profile after longer treatment exposure and follow-up.

AB - Introduction: The efficacy and safety of atezolizumab versus the efficacy and safety of docetaxel as second- or third-line treatment in patients with advanced NSCLC in the primary (n = 850) and secondary (n = 1225) efficacy populations of the randomized phase III OAK study (respectively referred to as the intention-to-treat [ITT] 850 [ITT850] and ITT1225) at an updated data cutoff were assessed. Methods: Patients received atezolizumab, 1200 mg, or docetaxel, 75 mg/m2, intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively. The primary end point was overall survival (OS) in the ITT population and programmed death-ligand 1–expressing subgroup. A sensitivity analysis was conducted to evaluate the impact of subsequent immunotherapy use in the docetaxel arm on the observed survival benefit with atezolizumab. Results: Atezolizumab demonstrated an OS benefit versus docetaxel in the updated ITT850 (hazard ratio [HR] = 0.75, 95% confidence interval: 0.64–0.89, p = 0.0006) and the ITT1225 (HR = 0.80, 95% confidence interval: 0.70–0.92, p = 0.0012) after minimum follow-up times of 26 and 21 months, respectively. Improved survival with atezolizumab was observed across programmed death-ligand 1 and histological subgroups. In the immunotherapy sensitivity analysis, the relative OS benefit with atezolizumab was slightly greater in the ITT850 (HR = 0.69) and ITT1225 (HR = 0.74) than the conventional OS estimate. Fewer patients receiving atezolizumab experienced grade 3 or 4 treatment-related adverse events (14.9%) than did patients receiving docetaxel (42.4%); no grade 5 adverse events related to atezolizumab were observed. Conclusions: The results of the updated ITT850 and initial ITT1225 analyses were consistent with those of the primary efficacy analysis demonstrating survival benefit with atezolizumab versus with docetaxel. Atezolizumab continued to demonstrate a favorable safety profile after longer treatment exposure and follow-up.

KW - Atezolizumab

KW - Cancer immunotherapy

KW - Checkpoint inhibitor

KW - Non–small cell lung cancer

KW - PD-L1

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U2 - 10.1016/j.jtho.2018.04.039

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