Original Article
Non–Small Cell Lung Cancer
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

https://doi.org/10.1016/j.jtho.2018.04.039Get rights and content
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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.

Keywords

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

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Disclosure: Dr. Fehrenbacher has received research funding from Roche/Genentech. Dr. von Pawel has been a consultant/advisor for Abbvie, Bristol-Myers Squibb, Novartis, and Pfizer. Dr. Park has been a consultant/advisor for Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Lilly, GlaxoSmithKline, Hanmi, Kyowa Hakko Kirin, Novartis, Ono Pharmaceutical, and Roche and has participated in speakers’ bureau for AstraZeneca and Boehringer Ingelheim. Dr. Rittmeyer has been a consultant/advisor for AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, MSD, Pfizer, and Roche/Genentech. Dr. Gandara has received research funding from Genentech and has been a consultant/advisor for Genentech. Dr. Han has received research funding from Roche, been a consultant/advisor for MSD Oncology, and received honoraria from Novartis. Dr. Gadgeel has received research funding from ACEA Biosciences, Acerta Pharma, AstraZeneca/MedImmune, Bristol-Myers Squibb, Clovis Oncology, Five Prime Therapeutics, Genentech/Roche, Halozyme, Incyte, Janssen Oncology, Merck, Millennium, Novartis, OncoMed, and Pfizer and has been a consultant/advisor for ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech/Roche, and Pfizer; in addition, he has participated in a speakers’ bureau for AstraZeneca and received travel support from ARIAD/Takeda and Genentech/Roche. Dr. Hida has received research funding from Abbvie, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Chugai Pharma, Clovis Oncology, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Ignyta, Kissei, Kyowa Hakko Kirin, Lilly, Nippon Boehringer Ingelheim, Merck Serono, MSD, Novartis, Ono Pharmaceutical, Pfizer, Servier, Taiho Pharmaceutical, and Takeda and has received honoraria from AstraZeneca, Bristol-Myers Squibb, Chugai Pharma, Clovis Oncology, Kissei, Lilly, MSD, Nippon Boehringer Ingelheim, Novartis, Ono Pharmaceutical, Pfizer, and Taiho Pharmaceutical. Dr. Cortinovis had been a consultant/advisor for Boehringer Ingelheim, MSD, Novartis, and Roche. Dr. De Marinis has been a consultant/advisor for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pfizer, and Roche. Dr. Gandhi, Mr. Danner, Dr. Matheny, Dr. Kowanetz, Dr. He is a former employee of Genentech/Roche, Dr. Felizzi, Dr. Patel, Dr. Sandler, and Dr. Ballinger are employees of Genentech/Roche, and Dr. Gandhi, Dr. Matheny, Dr. Kowanetz, Dr. Felizzi, Dr. Patel, Dr. Sandler, and Dr. Ballinger have stock and/or other ownership in Roche. Dr. Gandhi has stock and/or other ownership in Acadia Pharmaceuticals, Avalanche Biotech, Bristol-Myers Squibb, Clovis Oncology, Gilead Sciences, Merck, Neuroendocrine Biosciences, Spark Therapeutics, and Valeant Pharmaceuticals. Mr. Danner has stock and/or other ownership in Pfizer. Dr. Matheny has a patent with Stanford University. Dr. Kowanetz has a patent titled “Biomarkers and Methods of Treating PD-1– and PD-L1–Related Conditions.” Dr. He has stock/other ownership in Allergen, Amgen, and Gilead Sciences. Dr. Barlesi has received research funding from Roche/Genentech and has been a consultant/advisor for AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Lilly, Merck Serono, Novartis, Pfizer, Pierre Fabre, and Roche/Genentech; in addition, he has received honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Genentech/Roche, Lilly, Merck Serono, Novartis, Pfizer, and Pierre Fabre. The remaining authors declare no conflict of interest.