Journal article
Blood tumor mutational burden (bTMB) and tumor PD-L1 as predictive biomarkers of survival in MYSTIC: First-line durvalumab (D) ± tremelimumab (T) versus chemotherapy (CT) in metastatic (m) NSCLC.
- Rizvi, Naiyer A. Columbia University Medical Center, New York, NY;
- Cho, Byoung Chul Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea;
- Reinmuth, Niels Asklepios Lung Clinic, Munich-Gauting, Germany;
- Lee, Ki Hyeong Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea;
- Luft, Alexander Leningrad Regional Clinical Hospital, Oncology Department, Lunacharskogo Prospect, Russian Federation;
- Ahn, Myung-Ju Samsung Medical Center, Seoul, South Korea;
- van den Heuvel, Michel Department of Thoracic Oncology, Netherlands Cancer Institute (NKI), Amsterdam, Netherlands;
- Dols, Manuel Cobo Hospital Universitario Regional Málaga, Instituto de Investigaciones Biomédicas Málaga (IBIMA), Málaga, Spain;
- Vicente, David Hospital Universitario Virgen Macarena, Seville, Spain;
- Smolin, Alexey Main Military Hospital, Moscow, Russian Federation;
- Moiseyenko, Vladimir Clinical Research Center, Pesochny, St. Petersburg, Russian Federation;
- Antonia, Scott Joseph Moffitt Cancer Center, Tampa, FL;
- Nakagawa, Kazuhiko Kindai University Hospital, Osaka, Japan;
- Goldberg, Sarah B. Yale University School of Medicine, New Haven, CT;
- Kim, Edward S. Levine Cancer Institute, Charlotte, NC;
- Walker, Jill AstraZeneca, Cambridge, United Kingdom;
- Raja, Rajiv MedImmune, Gaithersburg, MD;
- Liu, Feng AstraZeneca, Gaithersburg, MD;
- Scheuring, Urban J. AstraZeneca, Cambridge, United Kingdom;
- Peters, Solange Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland;
Published in:
- Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2019, vol. 37, no. 15_suppl, p. 9016-9016
English
9016 Background: MYSTIC, an open-label, Ph3 trial of first-line D (anti-PD-L1) ± T (anti-CTLA-4) vs platinum-based CT, showed an improvement in OS with D vs CT in pts with tumor cell PD-L1 expression ≥25% (PD-L1 TC ≥25%; HR 0.76 [97.54% CI 0.56–1.02], p = 0.036). Exploratory analyses showed bTMB was a predictive biomarker for OS with D±T vs CT. We report further exploratory analyses of OS according to PD-L1 and bTMB. Methods: Immunotherapy/CT-naïve pts with mNSCLC were randomized (1:1:1) to D, D+T or CT. bTMB levels (mut/Mb) were evaluated with the GuardantOMNI platform (Guardant Health), and PD-L1 TC expression with the VENTANA PD-L1 (SP263) IHC assay. Results: D improved OS vs CT in pts with PD-L1 TC ≥25% across bTMB levels (PD-L1 TC ≥25%/bTMB≥20 HR 0.79 [95% CI 0.45, 1.39]; PD-L1 TC ≥25%/bTMB < 20 HR 0.64 [95% CI 0.45, 0.90]). In contrast, D+T improved OS vs CT in pts with bTMB≥20 across different PD-L1 TC expression levels (Table; PD-L1 TC ≥25%/bTMB≥20 HR 0.44 [95% CI 0.23, 0.84]; PD-L1 TC < 1%/bTMB≥20 HR 0.42 [95% CI 0.17, 0.97]). Additional cutoffs and outcomes in subgroups defined by both biomarkers will be presented. Conclusions: These exploratory analyses from MYSTIC support PD-L1 TC expression as an appropriate predictive biomarker for OS with D vs CT, while suggesting bTMB as a predictive biomarker for OS with D+T in mNSCLC. These biomarkers appear to be independent and both may be important for mNSCLC treatment decisions. Interpretation of these data may be limited by small sample sizes; further investigations are warranted. Clinical trial information: NCT02453282. [Table: see text]
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1200/jco.2019.37.15_suppl.9016
- ISSN 0732-183X
- Persistent URL
- https://sonar.ch/global/documents/78031
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