Beyond KRAS: Practical Molecular Targets in Pancreatic Adenocarcinoma

Grinshpun, Albert; Zarbiv, Yonaton; Roszik, Jason; Subbiah, Vivek; Hubert, Ayala

doi:10.1159/000496018

Cited by 15 publications

(11 citation statements)

References 17 publications

(22 reference statements)

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“…Five of them were treated with vemurafenib alone, resulting in 4 minimal tumor responses and 1 partial response [10, 11]. Two of them were treated with a combination of dabrafenib and trametinib, with 1 partial response and 1 minimal response [12]. Our patient had both BRAF and P53 mutations, consistent with the article mentioned above.…”

Section: Discussionsupporting

confidence: 74%

Metastatic Pancreatic Cancer with BRAF and P53 Mutations: Case Report of Therapeutic Response to Doublet Targeted Therapy

et al. 2020

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We report on the clinical history of a 49-year-old female with metastatic pancreatic cancer. She was initially treated with standard chemotherapy as per current guidelines. She was found to have both a BRAF and P53 mutation, and received dabrafenib and trametinib with deep responses, both radiographically and biochemically (CA19-9). Her response has been more clinically relevant than responses in previous case reports of patients with BRAF-positive pancreatic cancer treated with targeted therapy. To the best of our knowledge, this is the first case report showing a dramatic therapeutic response to combination therapy with dabrafenib and trametinib in metastatic pancreatic cancer.

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Section: Discussionsupporting

confidence: 74%

Metastatic Pancreatic Cancer with BRAF and P53 Mutations: Case Report of Therapeutic Response to Doublet Targeted Therapy

et al. 2020

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“…However, recurrence rates even after R0 resection remain unacceptably high [6][7][8][9][10]. The integration of more efficacious systemic chemotherapy regimens has improved median overall survival [11], yet responses of individual PDACs to chemotherapy are highly heterogeneous and personalization of perioperative therapy is in its infancy [12][13][14][15][16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

Longitudinal analysis of cell-free mutated KRAS and CA 19–9 predicts survival following curative resection of pancreatic cancer

et al. 2021

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Background Novel biomarkers and molecular monitoring tools hold potential to improve outcome for patients following resection of pancreatic ductal adenocarcinoma (PDAC). We hypothesized that the combined longitudinal analysis of mutated cell-free plasma KRAS (cfKRASmut) and CA 19–9 during adjuvant treatment and follow-up might more accurately predict disease course than hitherto available parameters. Methods Between 07/2015 and 10/2018, we collected 134 plasma samples from 25 patients after R0/R1-resection of PDAC during adjuvant chemotherapy and post-treatment surveillance at our institution. Highly sensitive discriminatory multi-target ddPCR assays were employed to screen plasma samples for cfKRASmut. cfKRASmut and CA 19–9 dynamics were correlated with recurrence-free survival (RFS) and overall survival (OS). Patients were followed-up until 01/2020. Results Out of 25 enrolled patients, 76% had undergone R0 resection and 48% of resected PDACs were pN0. 17/25 (68%) of patients underwent adjuvant chemotherapy. Median follow-up was 22.0 months, with 19 out of 25 (76%) patients relapsing during study period. Median RFS was 10.0 months, median OS was 22.0 months. Out of clinicopathologic variables, only postoperative CA 19–9 levels and administration of adjuvant chemotherapy correlated with survival endpoints. cfKRASmut. was detected in 12/25 (48%) of patients, and detection of high levels inversely correlated with survival endpoint. Integration of cfKRASmut and CA 19–9 levels outperformed either individual marker. cfKRASmut outperformed CA 19–9 as dynamic marker since increase during adjuvant chemotherapy and follow-up was highly predictive of early relapse and poor OS. Conclusions Integrated analysis of cfKRASmut and CA 19–9 levels is a promising approach for molecular monitoring of patients following resection of PDAC. Larger prospective studies are needed to further develop this approach and dissect each marker’s specific potential.

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“…Because of a BRAF mutation, they both were started on dabrafenib and trametinib. Both patients were on the treatment regimen briefly before passing away ( Grinshpun et al 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Potential benefit of treatment with MEK inhibitors and chemotherapy in BRAF-mutated KRAS wild-type pancreatic ductal adenocarcinoma patients: a case report

Ardalan

Azqueta

England

et al. 2021

Cold Spring Harb Mol Case Stud

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This is the first case report of a 60-yr-old female who underwent therapy for metastatic pancreatic cancer with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). Upon the progression of her disease, she was switched to gemcitabine and nab-paclitaxel. Per genomic sequencing, her tumor was found to be a KRAS wild-type and BRAF V600E mutation, which then warranted treatment with the MEK1 and MEK2 inhibitor, cobimetinib. The patient has achieved a complete response (CR) to a combination of gemcitabine, nab-paclitaxel, and cobimetinib. It has been 16 mo since the start of the treatment, and the patient continues to demonstrate a complete durable response both serologically and radiologically.

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Beyond KRAS: Practical Molecular Targets in Pancreatic Adenocarcinoma

Cited by 15 publications

References 17 publications

Metastatic Pancreatic Cancer with BRAF and P53 Mutations: Case Report of Therapeutic Response to Doublet Targeted Therapy

Metastatic Pancreatic Cancer with BRAF and P53 Mutations: Case Report of Therapeutic Response to Doublet Targeted Therapy

Longitudinal analysis of cell-free mutated KRAS and CA 19–9 predicts survival following curative resection of pancreatic cancer

Potential benefit of treatment with MEK inhibitors and chemotherapy in BRAF-mutated KRAS wild-type pancreatic ductal adenocarcinoma patients: a case report

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