Correlation of pre- and post-induction plasma mutant allele fraction with progression-free survival (PFS) in STEAM, a prospective, randomized, multicenter study in metastatic colorectal cancer (mCRC)
| Autor: | John F. Palma, Christoph Mancao, Alan Nicholas, Carolyn Williams, May Yau, Nasiema Wingate-Pearse, Lijing Yao, Nicolas Sommer, Monica Pimentel, David Zhang, Johanna C. Bendell, John Lee, Abraham Munoz, Stephanie J. Yaung, Katrina Mayol, Herbert Hurwitz, Alexander F. Lovejoy, Ulrich Peter Rohr |
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| Rok vydání: | 2017 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Colorectal cancer business.industry Mutant allele medicine.disease Correlation 03 medical and health sciences 0302 clinical medicine Multicenter study 030220 oncology & carcinogenesis Internal medicine medicine Progression-free survival business Pre and post 030215 immunology |
| Zdroj: | Journal of Clinical Oncology. 35:e15118-e15118 |
| ISSN: | 1527-7755 0732-183X 0176-5582 |
| DOI: | 10.1200/jco.2017.35.15_suppl.e15118 |
| Popis: | e15118 Background: STEAM (NCT01765582) evaluated the efficacy and safety of concurrent (c) and sequential (s) FOLFOXIRI-bevacizumab (BEV) versus FOLFOX-BEV for first-line treatment of mCRC. Methods: The AVENIO ctDNA Expanded Kit (Research Use Only) was used to identify somatic mutations in 77 cancer-related genes by next-generation sequencing (NGS) in both pre- and post-induction plasma samples (n = 118 for both groups) from STEAM. Demographics for patient tested were similar to the overall cohort. The mutant allele fraction (mAF) represents the mutation frequency in ctDNA for single nucleotide variants (SNVs) and indels detected per patient. Results: Overall, patients with a pre-induction mAF below the median had longer PFS compared to patients with mAF above the median (13.4 vs 9.5 mo, HR 0.49, p = 0.002). A similar trend was seen for overall survival (OS). Within the below median mAF group, longer PFS was observed in patients treated with cFOLFOXIRI-BEV versus FOLFOX-BEV (25.2 vs 9.5 mo, HR 0.34, p = 0.020). In contrast, no differences in PFS were observed in the treatment arms in the above median mAF group. Patients with a post-induction mAF below the median had longer PFS compared to patients with mAF above the median (15.3 vs 8.1 mo, HR 0.51, p = 0.0064). Correlations of post-induction genomic changes with outcomes, according to treatment groups, will also be presented. Conclusions: The level of pre- and post-induction mAF appears to correlate with PFS in STEAM overall. Furthermore, a lower median pre-induction mAF suggests PFS benefit for cFOLFOXIRI-BEV versus FOLFOX-BEV. Thus, plasma analysis of mAF via the AVENIO ctDNA Expanded Kit may identify patients who benefit from specific treatment in mCRC. These results are hypothesis generating and require further clinical validation. Clinical trial information: NCT01765582. |
| Databáze: | OpenAIRE |
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