David R Gandara1, Joachim von Pawel2, Julien Mazieres3, Richard Sullivan4, Åslaug Helland5, Ji-Youn Han6, Santiago Ponce Aix7, Achim Rittmeyer8, Fabrice Barlesi9, Toshio Kubo10, Keunchil Park11, Jerome Goldschmidt12, Mayank Gandhi13, Cindy Yun13, Wei Yu13, Christina Matheny13, Pei He14, Alan Sandler13, Marcus Ballinger13, Louis Fehrenbacher15. 1. UC Davis Comprehensive Cancer Center, Sacramento, California. Electronic address: drgandara@ucdavis.edu. 2. Asklepios-Fachkliniken München-Gauting, Gauting, Germany. 3. Toulouse University Hospital, Toulouse, France. 4. Auckland City Hospital, Auckland, New Zealand. 5. Oslo University Hospital, University of Oslo, Oslo, Norway. 6. National Cancer Center, Ilsandong-gu, Goyang, Korea. 7. Hospital Universitario 12 de Octubre, Madrid, Spain. 8. Lungenfachklinik Immenhausen, Immenhausen, Germany. 9. Aix Marseille University; Assistance Publique Hôpitaux de Marseille, Marseille, France. 10. Okayama University Hospital, Okayama, Japan. 11. Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Korea. 12. Blue Ridge Cancer Care, Blacksburg, Virginia; US Oncology Research, The Woodlands, Texas. 13. Genentech, Inc., South San Francisco, California. 14. Blue Ridge Cancer Care, Blacksburg, Virginia; US Oncology Research, The Woodlands, Texas; Genentech, Inc., South San Francisco, California. 15. Kaiser Permanente Medical Center, Vallejo, California.
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.
RCT Entities:
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 atezolizumabTBPpatients, 7% achieved a post-progression response in target lesions and 49% had stable target lesions. AtezolizumabTBP 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 atezolizumabTBP in patients performing well clinically at the time of PD.
Authors: Giulio Metro; Alfredo Addeo; Diego Signorelli; Alessio Gili; Panagiota Economopoulou; Fausto Roila; Giuseppe Banna; Alessandro De Toma; Juliana Rey Cobo; Andrea Camerini; Athina Christopoulou; Giuseppe Lo Russo; Marco Banini; Domenico Galetta; Beatriz Jimenez; Ana Collazo-Lorduy; Antonio Calles; Panagiotis Baxevanos; Helena Linardou; Paris Kosmidis; Marina C Garassino; Giannis Mountzios Journal: J Thorac Dis Date: 2019-12 Impact factor: 2.895
Authors: Jeffrey C Thompson; Erica L Carpenter; Benjamin A Silva; Jamie Rosenstein; Austin L Chien; Katie Quinn; Carin R Espenschied; Allysia Mak; Lesli A Kiedrowski; Martina Lefterova; Rebecca J Nagy; Sharyn I Katz; Stephanie S Yee; Taylor A Black; Aditi P Singh; Christine A Ciunci; Joshua M Bauml; Roger B Cohen; Corey J Langer; Charu Aggarwal Journal: JCO Precis Oncol Date: 2021-03-19
Authors: Roberto Ferrara; Diego Signorelli; Claudia Proto; Arsela Prelaj; Marina Chiara Garassino; Giuseppe Lo Russo Journal: Transl Lung Cancer Res Date: 2021-06