Abstract 399: ctDNA a promising predictive marker for treatment with PD-1 inhibitors in KRAS mutated NSCLC after platinum based chemotherapy
| Autor: | Lucie Hijmering-Kappelle, Birgitta. L. Hiddinga, Harry J.M. Groen, T. Jeroen N. Hiltermann, Ed Schuuring, Anthonie J. van der Wekken, Maria L. Aguirre Azpurua, Wim Timens |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Cancer Research. 79:399-399 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2019-399 |
| Popis: | Introduction: Immunotherapy is a breakthrough in non-small cell lung cancer (NSCLC), showing long lasting responses in metastasized disease. However, only a limited number of patients responds to treatment. Selection of patients by known biomarkers (eg PD-L1, TMB) and combining PD-(L)1 inhibitors with other treatments (eg. chemotherapy or CTLA4 inhibitors) enriches the population for responders, however still around 60% do not respond with a durable response. We hypothesized that in KRAS mutant positive advanced NSCLC the detection of changes of ctDNA levels will be a relevant predictive marker in immunotherapy ( and stronger than eg PD-L1 expression in tumor tissue).. Purpose: To test ctDNA as an early predictive marker for durable response in KRAS mutated lung cancer, in patients treated with PD-1 inhibitors after progression on platinum containing chemotherapy. Methods: Patients with advanced NSCLC treated with nivolumab with a known KRAS or BRAF mutation from primary biopsy, with disease progression after platinum based chemotherapy are eligible. ctDNA obtained from EDTA plasma at baseline, 1, 2, 4, 6 weeks and thereafter every 12 weeks compared to durable response as primary outcome (ie. benefit from treatment> 6month). Secondary outcomes were tumor response according to RECISTv1.1, progression-free and overall survival. ctDNA was determined and analyzed using a digital droplet PCR assay (Biorad) that was confirmed by a second technique (Idylla). ctDNA was categorized according to its response pattern in time: increasing, decreasing and undetectable KRAS mutant allele frequencies over time. Results: In this ongoing study 31 patients with a known KRAS and 2 patients with a BRAF mutation participated. 24 (72%) had detectable levels of KRAS (n=22) or BRAF (n=2) in plasma. Concordance between Idylla and ddPCR was good and correlation was high (R2 =0,52). Of first 27 patients ctDNA increasing n=11, decreasing n=10, no change n=6. Data on all included patients will be presented. Conclusion: Early detection of decreasing KRAS/BRAF mutant alleles in ctDNA predicted durable tumor responses, and increasing levels were associated with early disease progression. Citation Format: T.Jeroen.N. Hiltermann, Lucie B.M. Hijmering-Kappelle, Maria L. Aguirre Azpurua, Anthonie.J. vd Wekken, Birgitta.I. Hiddinga, Wim Timens, Harry.J.M. Groen, Ed Schuuring. ctDNA a promising predictive marker for treatment with PD-1 inhibitors in KRAS mutated NSCLC after platinum based chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 399. |
| Databáze: | OpenAIRE |
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