Abstract 1285P
Background
Interstitial pneumonia (IP) is a common and poor prognostic comorbidity in patients with non-small cell lung cancer (NSCLC) and is also a risk factor for pneumonitis. A phase II trial of atezolizumab for pretreated NSCLC patients with comorbid idiopathic IP (TORG1936/AMBITIOUS study) was terminated early due to the high incidence of severe pneumonitis. While safety information has already been published, we will report the results of the final analysis including efficacy and results of translational study.
Methods
This study is the multicenter, single-arm, phase II trial to evaluate the efficacy and safety of atezolizumab for pretreated advanced or recurrent NSCLC patients with idiopathic, chronic fibrotic interstitial pneumonia with a predicted forced vital capacity (%FVC) > 70%, with or without honeycomb lung on chest computed tomography. The enrolled patients received atezolizumab (1200 mg) every three weeks until the discontinuation criteria are satisfied. The primary end point was the 1-year survival rate. A sample size of 38 patients was set (expected value of 40% and a threshold value of 15%, two-sided α = 0.05; 1-β = 0.9). As a translational research, we performed the analysis of tumor mutation burden (TMB) and somatic mutations from tumor samples.
Results
A total of 17 patients were eventually registered, with a median age of 70 years, and a median %FVC of 85.4%. 41.1% (7/17) of patients had honeycomb lungs. One-year survival rate was 53.3% (95% confidence interval [CI]; 25.9 – 74.6). Median overall survival and progression free survival time were 15.3 months (95% CI; 3.1 – Not Reached) and 3.2 months (95% CI; 1.2 – 7.4), respectively. The incidence of pneumonitis within 1 year after initiation of atezolizumab was 29.4% (5/17) for all grade, and 23.5% (4/17) for grade ≥ 3. Neither TMB nor any of the detected somatic mutations (e.g., TP53 and KRAS) were associated with efficacy or risk of pneumonitis.
Conclusions
Atezolizumab for NSCLC with comorbid interstitial pneumonia may provide survival benefit, despite the high risk of developing pneumonitis. Further clinical studies to identify risk factors for pneumonitis is warranted for appropriate patient selection.
Clinical trial identification
jRCTs031190084.
Editorial acknowledgement
Legal entity responsible for the study
Thoracic Oncology Research Group.
Funding
Chugai Pharmaceutical Co., Ltd.
Disclosure
Y. Sato: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Ono; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Nippon Kayaku; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb. S. Ikeda: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Ono; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Thermo Fisher Scientific; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: AstraZeneca. T. Kato: Financial Interests, Personal, Invited Speaker: AbbVie; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AbbVie; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. H. Kenmotsu: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Ono; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Kyowa Hakko Kirin; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: Novartis Pharma; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca. T. Ogura: Financial Interests, Personal, Invited Speaker: Shionogi; Financial Interests, Personal, Invited Speaker: Nippon Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Research Grant: Chugai. T. Tokito: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD. I. Okamoto: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Research Grant: Chugai. N. Furuya: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Kyowa Hakko Kirin; Financial Interests, Personal, Invited Speaker: Pfizer. T. Yokoyama: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: Delta-Fly Pharma; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Eli Lilly Japan. T. Iwasawa: Financial Interests, Personal, Speaker’s Bureau: Canon Medical Systems; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Canon Medical Systems. T. Yamanaka: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Otsuka; Financial Interests, Personal, Invited Speaker: Ono; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Gilead Sciences; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: EPS. H. Okamoto: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Kyorin; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Merck BioPharma. All other authors have declared no conflicts of interest.