Atezolizumab Treatment Beyond Progression in Advanced NSCLC: Results From the Randomized, Phase III OAK Study

David R. Gandara, Joachim von Pawel, Julien Mazieres, Richard Sullivan, Åslaug Helland, Ji Youn Han, Santiago Ponce Aix, Achim Rittmeyer, Fabrice Barlesi, Toshio Kubo, Keunchil Park, Jerome Goldschmidt, Mayank Gandhi, Cindy Yun, Wei Yu, Christina Matheny, Pei He, Alan Sandler, Marcus Ballinger, Louis Fehrenbacher

Research output: Contribution to journalArticle

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Abstract

Introduction: Cancer immunotherapy may alter tumor biology such that treatment effects can extend beyond radiographic progression. In the randomized, phase III OAK study of atezolizumab (anti–programmed death-ligand 1) versus docetaxel in advanced NSCLC, overall survival (OS) benefit with atezolizumab was observed in the overall patient population, without improvement in objective response rate (ORR) or progression-free survival (PFS). We examine the benefit-risk of atezolizumab treatment beyond progression (TBP). Methods: Eight hundred fifty patients included in the OAK primary efficacy analysis were evaluated. Atezolizumab was continued until loss of clinical benefit. Docetaxel was administered until Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) disease progression (PD)/unacceptable toxicity; no crossover to atezolizumab was allowed. ORR, PFS, post-PD OS, target lesion change, and safety were evaluated. Results: In atezolizumab-arm patients, ORR was 16% versus 14% and median PFS was 4.2 versus 2.8 months per immune-modified RECIST versus RECIST v1.1. The median post-PD OS was 12.7 months (95% confidence interval [CI]: 9.3–14.9) in 168 atezolizumab-arm patients continuing TBP, 8.8 months (95% CI: 6.0–12.1) in 94 patients switching to nonprotocol therapy, and 2.2 months (95% CI: 1.9–3.4) in 70 patients receiving no further therapy. Of the atezolizumab TBP patients, 7% achieved a post-progression response in target lesions and 49% had stable target lesions. Atezolizumab TBP was not associated with increased safety risks. Conclusions: Within the limitations of this retrospective analysis, the post-PD efficacy and safety data from OAK are consistent with a positive benefit-risk profile of atezolizumab TBP in patients performing well clinically at the time of PD.

Original languageEnglish
JournalJournal of Thoracic Oncology
DOIs
Publication statusAccepted/In press - Jan 1 2018

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docetaxel
Disease-Free Survival
Therapeutics
Confidence Intervals
Safety
Survival
MPDL3280A
Immunotherapy
Disease Progression
Neoplasms
Ligands
Population
Response Evaluation Criteria in Solid Tumors

Keywords

  • Atezolizumab
  • Immune checkpoint therapy beyond disease progression
  • NSCLC

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Gandara, D. R., von Pawel, J., Mazieres, J., Sullivan, R., Helland, Å., Han, J. Y., ... Fehrenbacher, L. (Accepted/In press). Atezolizumab Treatment Beyond Progression in Advanced NSCLC: Results From the Randomized, Phase III OAK Study. Journal of Thoracic Oncology. https://doi.org/10.1016/j.jtho.2018.08.2027

Atezolizumab Treatment Beyond Progression in Advanced NSCLC : Results From the Randomized, Phase III OAK Study. / Gandara, David R.; von Pawel, Joachim; Mazieres, Julien; Sullivan, Richard; Helland, Åslaug; Han, Ji Youn; Ponce Aix, Santiago; Rittmeyer, Achim; Barlesi, Fabrice; Kubo, Toshio; Park, Keunchil; Goldschmidt, Jerome; Gandhi, Mayank; Yun, Cindy; Yu, Wei; Matheny, Christina; He, Pei; Sandler, Alan; Ballinger, Marcus; Fehrenbacher, Louis.

In: Journal of Thoracic Oncology, 01.01.2018.

Research output: Contribution to journalArticle

Gandara, DR, von Pawel, J, Mazieres, J, Sullivan, R, Helland, Å, Han, JY, Ponce Aix, S, Rittmeyer, A, Barlesi, F, Kubo, T, Park, K, Goldschmidt, J, Gandhi, M, Yun, C, Yu, W, Matheny, C, He, P, Sandler, A, Ballinger, M & Fehrenbacher, L 2018, 'Atezolizumab Treatment Beyond Progression in Advanced NSCLC: Results From the Randomized, Phase III OAK Study', Journal of Thoracic Oncology. https://doi.org/10.1016/j.jtho.2018.08.2027
Gandara, David R. ; von Pawel, Joachim ; Mazieres, Julien ; Sullivan, Richard ; Helland, Åslaug ; Han, Ji Youn ; Ponce Aix, Santiago ; Rittmeyer, Achim ; Barlesi, Fabrice ; Kubo, Toshio ; Park, Keunchil ; Goldschmidt, Jerome ; Gandhi, Mayank ; Yun, Cindy ; Yu, Wei ; Matheny, Christina ; He, Pei ; Sandler, Alan ; Ballinger, Marcus ; Fehrenbacher, Louis. / Atezolizumab Treatment Beyond Progression in Advanced NSCLC : Results From the Randomized, Phase III OAK Study. In: Journal of Thoracic Oncology. 2018.
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abstract = "Introduction: Cancer immunotherapy may alter tumor biology such that treatment effects can extend beyond radiographic progression. In the randomized, phase III OAK study of atezolizumab (anti–programmed death-ligand 1) versus docetaxel in advanced NSCLC, overall survival (OS) benefit with atezolizumab was observed in the overall patient population, without improvement in objective response rate (ORR) or progression-free survival (PFS). We examine the benefit-risk of atezolizumab treatment beyond progression (TBP). Methods: Eight hundred fifty patients included in the OAK primary efficacy analysis were evaluated. Atezolizumab was continued until loss of clinical benefit. Docetaxel was administered until Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) disease progression (PD)/unacceptable toxicity; no crossover to atezolizumab was allowed. ORR, PFS, post-PD OS, target lesion change, and safety were evaluated. Results: In atezolizumab-arm patients, ORR was 16{\%} versus 14{\%} and median PFS was 4.2 versus 2.8 months per immune-modified RECIST versus RECIST v1.1. The median post-PD OS was 12.7 months (95{\%} confidence interval [CI]: 9.3–14.9) in 168 atezolizumab-arm patients continuing TBP, 8.8 months (95{\%} CI: 6.0–12.1) in 94 patients switching to nonprotocol therapy, and 2.2 months (95{\%} CI: 1.9–3.4) in 70 patients receiving no further therapy. Of the atezolizumab TBP patients, 7{\%} achieved a post-progression response in target lesions and 49{\%} had stable target lesions. Atezolizumab TBP was not associated with increased safety risks. Conclusions: Within the limitations of this retrospective analysis, the post-PD efficacy and safety data from OAK are consistent with a positive benefit-risk profile of atezolizumab TBP in patients performing well clinically at the time of PD.",
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T2 - Results From the Randomized, Phase III OAK Study

AU - Gandara, David R.

AU - von Pawel, Joachim

AU - Mazieres, Julien

AU - Sullivan, Richard

AU - Helland, Åslaug

AU - Han, Ji Youn

AU - Ponce Aix, Santiago

AU - Rittmeyer, Achim

AU - Barlesi, Fabrice

AU - Kubo, Toshio

AU - Park, Keunchil

AU - Goldschmidt, Jerome

AU - Gandhi, Mayank

AU - Yun, Cindy

AU - Yu, Wei

AU - Matheny, Christina

AU - He, Pei

AU - Sandler, Alan

AU - Ballinger, Marcus

AU - Fehrenbacher, Louis

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N2 - Introduction: Cancer immunotherapy may alter tumor biology such that treatment effects can extend beyond radiographic progression. In the randomized, phase III OAK study of atezolizumab (anti–programmed death-ligand 1) versus docetaxel in advanced NSCLC, overall survival (OS) benefit with atezolizumab was observed in the overall patient population, without improvement in objective response rate (ORR) or progression-free survival (PFS). We examine the benefit-risk of atezolizumab treatment beyond progression (TBP). Methods: Eight hundred fifty patients included in the OAK primary efficacy analysis were evaluated. Atezolizumab was continued until loss of clinical benefit. Docetaxel was administered until Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) disease progression (PD)/unacceptable toxicity; no crossover to atezolizumab was allowed. ORR, PFS, post-PD OS, target lesion change, and safety were evaluated. Results: In atezolizumab-arm patients, ORR was 16% versus 14% and median PFS was 4.2 versus 2.8 months per immune-modified RECIST versus RECIST v1.1. The median post-PD OS was 12.7 months (95% confidence interval [CI]: 9.3–14.9) in 168 atezolizumab-arm patients continuing TBP, 8.8 months (95% CI: 6.0–12.1) in 94 patients switching to nonprotocol therapy, and 2.2 months (95% CI: 1.9–3.4) in 70 patients receiving no further therapy. Of the atezolizumab TBP patients, 7% achieved a post-progression response in target lesions and 49% had stable target lesions. Atezolizumab TBP was not associated with increased safety risks. Conclusions: Within the limitations of this retrospective analysis, the post-PD efficacy and safety data from OAK are consistent with a positive benefit-risk profile of atezolizumab TBP in patients performing well clinically at the time of PD.

AB - Introduction: Cancer immunotherapy may alter tumor biology such that treatment effects can extend beyond radiographic progression. In the randomized, phase III OAK study of atezolizumab (anti–programmed death-ligand 1) versus docetaxel in advanced NSCLC, overall survival (OS) benefit with atezolizumab was observed in the overall patient population, without improvement in objective response rate (ORR) or progression-free survival (PFS). We examine the benefit-risk of atezolizumab treatment beyond progression (TBP). Methods: Eight hundred fifty patients included in the OAK primary efficacy analysis were evaluated. Atezolizumab was continued until loss of clinical benefit. Docetaxel was administered until Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) disease progression (PD)/unacceptable toxicity; no crossover to atezolizumab was allowed. ORR, PFS, post-PD OS, target lesion change, and safety were evaluated. Results: In atezolizumab-arm patients, ORR was 16% versus 14% and median PFS was 4.2 versus 2.8 months per immune-modified RECIST versus RECIST v1.1. The median post-PD OS was 12.7 months (95% confidence interval [CI]: 9.3–14.9) in 168 atezolizumab-arm patients continuing TBP, 8.8 months (95% CI: 6.0–12.1) in 94 patients switching to nonprotocol therapy, and 2.2 months (95% CI: 1.9–3.4) in 70 patients receiving no further therapy. Of the atezolizumab TBP patients, 7% achieved a post-progression response in target lesions and 49% had stable target lesions. Atezolizumab TBP was not associated with increased safety risks. Conclusions: Within the limitations of this retrospective analysis, the post-PD efficacy and safety data from OAK are consistent with a positive benefit-risk profile of atezolizumab TBP in patients performing well clinically at the time of PD.

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