TY - JOUR
T1 - Atezolizumab Treatment Beyond Progression in Advanced NSCLC
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
N1 - Funding Information:
This work was supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland/Genentech, Inc., South San Francisco, California. F. Hoffmann-La Roche Ltd/Genentech, Inc., was involved in study design; the collection, analysis, and interpretation of data; the writing of the report; and the decision to submit the article for publication in conjunction with the authors. The authors thank Daniel Waterkamp of Genentech, Inc., for contribution to the OAK study design, execution, and data interpretation; and Shiyao Liu of Genentech, Inc., for contribution to the data analysis methodology. Third-party medical writing support was provided by Meghal Gandhi, PhD, (Health Interactions, Inc.), with funding from F. Hoffmann-La Roche, Ltd.
Funding Information:
Disclosure: Dr. Gandara has received grants from Genentech and personal fees from Genentech, AstraZeneca, and Merck. Dr. von Pawel has received personal fees from Novartis, Abbvie, Pfizer, and Bristol Myers Squibb. Dr. Mazieres has received personal fees from Roche/Genentech, Bristol Myers Squibb, Astra Zeneca, Novartis, Pfizer, Lilly/ImClone, and MSD. Dr. Helland has received research support from F. Hoffmann-La Roche and personal fees from F. Hoffmann-La Roche, AstraZeneca and Takeda. Dr. Han has received personal fees from Novartis and MSD Oncology; and has received grants from Roche. Dr. Rittmeyer has received personal fees from Lilly, Bristol Myers Squibb, Boehringer Ingelheim, Astra Zeneca, MSD, Pfizer, AbbVie, and Roche/Genentech. Dr. Barlesi has received personal fees from Astra Zeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd., Novartis, Merck, MSD, Pierre Fabre, Pfizer, and Takeda. Dr. Park has received personal fees from Astellas Pharma, Astra Zeneca, Boehringer Ingelheim, Clovis Oncology, Lilly, Hanmi, Kyowa Hakko Kirin, Novartis, Ono Pharmaceutical, Roche, Bristol-Myers Squibb, and GlaxoSmithKline. Dr. Goldschmidt has received personal fees from Amgen, Bristol-Myers Squibb, and Celgene. Drs. Gandhi, Yun, Yu, Matheny, He, Sandler, and Ballinger are employees with Roche/Genentech. Dr. Gandhi has reported stock/other ownership in Acadia Pharmaceuticals, Avalanche Biotech, Bristol-Myers Squibb, Clovis Oncology, Gilead Sciences, Merck, Neuroendocrine Biosciences, Spark Therapeutics, and Valeant Pharmaceuticals. Dr. Matheny has received support from Roche ; and has a patent pending at Stanford. Dr. He has received personal fees from Genentech/Roche; and has reported stock/other ownership in Amgen , Gilead Sciences, and Allergan. Dr. Sandler has reported stock/other ownership in F. Hoffmann-La Roche Ltd. Dr. Ballinger has received personal fees from Genentech/Roche; and has received other support from Roche. Dr. Fehrenbacher has received a grant from Roche/Genentech . The remaining authors declare no additional conflicts of interest.
Funding Information:
Disclosure: Dr. Gandara has received grants from Genentech and personal fees from Genentech, AstraZeneca, and Merck. Dr. von Pawel has received personal fees from Novartis, Abbvie, Pfizer, and Bristol Myers Squibb. Dr. Mazieres has received personal fees from Roche/Genentech, Bristol Myers Squibb, Astra Zeneca, Novartis, Pfizer, Lilly/ImClone, and MSD. Dr. Helland has received research support from F. Hoffmann-La Roche and personal fees from F. Hoffmann-La Roche, AstraZeneca and Takeda. Dr. Han has received personal fees from Novartis and MSD Oncology; and has received grants from Roche. Dr. Rittmeyer has received personal fees from Lilly, Bristol Myers Squibb, Boehringer Ingelheim, Astra Zeneca, MSD, Pfizer, AbbVie, and Roche/Genentech. Dr. Barlesi has received personal fees from Astra Zeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd., Novartis, Merck, MSD, Pierre Fabre, Pfizer, and Takeda. Dr. Park has received personal fees from Astellas Pharma, Astra Zeneca, Boehringer Ingelheim, Clovis Oncology, Lilly, Hanmi, Kyowa Hakko Kirin, Novartis, Ono Pharmaceutical, Roche, Bristol-Myers Squibb, and GlaxoSmithKline. Dr. Goldschmidt has received personal fees from Amgen, Bristol-Myers Squibb, and Celgene. Drs. Gandhi, Yun, Yu, Matheny, He, Sandler, and Ballinger are employees with Roche/Genentech. Dr. Gandhi has reported stock/other ownership in Acadia Pharmaceuticals, Avalanche Biotech, Bristol-Myers Squibb, Clovis Oncology, Gilead Sciences, Merck, Neuroendocrine Biosciences, Spark Therapeutics, and Valeant Pharmaceuticals. Dr. Matheny has received support from Roche; and has a patent pending at Stanford. Dr. He has received personal fees from Genentech/Roche; and has reported stock/other ownership in Amgen, Gilead Sciences, and Allergan. Dr. Sandler has reported stock/other ownership in F. Hoffmann-La Roche Ltd. Dr. Ballinger has received personal fees from Genentech/Roche; and has received other support from Roche. Dr. Fehrenbacher has received a grant from Roche/Genentech. The remaining authors declare no additional conflicts of interest.
Publisher Copyright:
© 2018 International Association for the Study of Lung Cancer
PY - 2018/12
Y1 - 2018/12
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.
KW - Atezolizumab
KW - Immune checkpoint therapy beyond disease progression
KW - NSCLC
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UR - http://www.scopus.com/inward/citedby.url?scp=85055081542&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2018.08.2027
DO - 10.1016/j.jtho.2018.08.2027
M3 - Article
C2 - 30217492
AN - SCOPUS:85055081542
SN - 1556-0864
VL - 13
SP - 1906
EP - 1918
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 12
ER -
