Journal article
Circulating free DNA as a prognostic biomarker in patients with advanced ALK+ NSCLC treated with alectinib from the global phase III ALEX trial.
- Dziadziuszko, Rafal Medical University of Gdańsk, Department of Oncology and Radiotherapy, Gdańsk, Poland;
- Peters, Solange Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland;
- Mok, Tony S. K. Prince of Wales Hospital, Hong Kong, China;
- Camidge, D. Ross University of Colorado Cancer Center, Aurora, CO;
- Noé, Johannes F. Hoffmann-La Roche Ltd., Basel, Switzerland;
- Nowicka, Malgorzata F. Hoffmann-La Roche Ltd., Basel, Switzerland;
- Bordogna, Walter F. Hoffmann-La Roche Ltd., Basel, Switzerland;
- Morcos, Peter N. Roche Innovation Center, New York, NY;
- Smoljanovic, Vlatka F. Hoffmann-La Roche Ltd., Basel, Switzerland;
- Shaw, Alice Tsang Massachusetts General Hospital/Harvard Medical School, Boston, MA;
Published in:
- Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2019, vol. 37, no. 15_suppl, p. 9053-9053
English
9053 Background: Circulating free DNA (cfDNA) released predominantly by tumors into the blood correlates with tumor load, but correlation with outcomes after ALK inhibitor treatment is poorly understood. Here, we examine the prognostic potential of cfDNA in the phase III ALEX trial of alectinib versus crizotinib in previously untreated patients with advanced ALK+ NSCLC. Methods: Data cutoff was December 1, 2017. Median cfDNA was determined from 276 baseline samples; patients were stratified into ‘≤median’ and ‘ > median’ biomarker-evaluable populations (BEP). Results: Median cfDNA was 11.5ng/mL. Baseline characteristics were mostly balanced between the crizotinib (≤median, n = 72; > median, n = 67) and alectinib (≤median, n = 66; > median n = 71) BEPs. However, the alectinib > median BEP had more active smokers (7.0% vs crizotinib 1.5%), more measurable/non-measurable CNS lesions (47.9% vs 41.8%) and more patients with TP53 short-variant (SV) (44.8% vs 32.8%); the alectinib ≤median BEP had more active smokers (7.6% vs crizotinib 2.8%). Alectinib exposure was not substantially different between relevant BEPs. Higher cfDNA amount was associated with measurable/non-measurable CNS lesions and TP53 SV. Tumor burden positively correlated with normalized cfDNA amount (Pearson correlation 0.204; p < 0.001). Median PFS by investigator in the ≤median BEP was 34.9 months alectinib vs 14.8 crizotinib (HR 0.37, 95% CI 0.22–0.61, p < 0.0001); in the > median BEP it was 14.8 months alectinib vs 8.6 crizotinib (HR 0.43, 95% CI 0.28–0.64, p < 0.0001). Response rates in the ≤median BEP were 82.3% alectinib vs 70.4% crizotinib; in the > median BEP, 70.2% alectinib vs 55.4% crizotinib. Median duration of response in the ≤median BEP was not reached for alectinib vs 21.0 months for crizotinib; in the > median BEP, 33.1 months alectinib vs 7.3 crizotinib. Conclusions: Tumor burden positively correlated with cfDNA amount; patients with ≤median cfDNA at baseline had better prognosis than those with > median cfDNA. Alectinib consistently improved PFS, DOR and ORR versus crizotinib across BEPs, reducing the risk of tumor progression by > 50% compared with crizotinib. Clinical trial information: NCT02075840.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1200/jco.2019.37.15_suppl.9053
- ISSN 0732-183X
- Persistent URL
- https://sonar.rero.ch/global/documents/84823
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