Durable response to first-line PARP inhibition in -mutated metastatic cholangiocarcinoma: case report.

Background: Cholangiocarcinoma (CCA) is an increasingly prevalent malignancy worldwide, with poor outcomes even when diagnosed at an early stage. While recent trials have shown benefit from the addition of immunotherapy to standard-of-care chemotherapy, the improvement in overall survival is modest. Multiple novel therapies for advanced CCA targeting actionable genetic alterations have been approved in recent years; mutations are identified in up to 5% of CCA patients and may be an additional target for novel treatment approaches.

A Real-World Comparison of Regorafenib and Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer in the United States.

Background: Trifluridine/Tipiracil (TAS-102) and regorafenib are FDA-approved in the United States for treatment of refractory metastatic colorectal cancer (mCRC). FDA approvals of these agents were based on modest improvements in overall survival (OS) compared with best supportive care + placebo in the RECOURSE and CORRECT trials, respectively. This study compared real-world clinical outcomes with the use of these agents.

Treatment outcomes in recurrent versus de novo metastatic pancreatic adenocarcinoma: a real world study.

Background: A majority of patients undergoing curative intent surgery for pancreatic ductal adenocarcinoma (PDAC) will unfortunately develop recurrent disease. Treatment outcomes for patients with metastatic disease remain suboptimal. In this study, we evaluated clinical outcomes of patients with recurrent PDAC who received systemic therapy and compared outcomes to patients with de novo metastatic PDAC undergoing systemic therapy.

Real-World Outcomes of Patients With BRAF-Mutated Metastatic Colorectal Cancer Treated in the United States.

Background: BRAF mutations portend a poor prognosis in metastatic colorectal cancer (mCRC). Whether these patients may benefit from more aggressive frontline chemotherapy with a triplet regimen such as FOLFOXIRI remains unclear. We used real-world data from a cohort of patients in the United States to assess the BRAF testing rate, determine the prevalence of FOLFOXIRI use, and compare survival outcomes in mCRC, stratified by BRAF mutation status and first-line therapy.

Treatment Trends and Clinical Outcomes of Left-Sided RAS/RAF Wild-Type Metastatic Colorectal Cancer in the United States.

Background: Post hoc analysis of the CALGB/SWOG 80405 trial suggests that anti-EGFR therapy may be superior to bevacizumab when added to first-line chemotherapy in patients with metastatic colorectal cancer (mCRC) who have left-sided primary tumors. We evaluated trends in use of anti-EGFR agents in patients with left-sided RAS/RAF wild-type (WT) mCRC and compared clinical outcomes among the most commonly used treatment strategies.

Methods: A nationwide electronic health record (EHR)-derived deidentified database was reviewed for patients with left-sided RAS/RAF WT mCRC.

Updates on adjuvant and neoadjuvant treatment strategies for surgically resectable and borderline resectable pancreatic ductal adenocarcinoma.

Pancreatic cancer is the third leading cause of cancer-related mortality in the US. Outcomes for patients with pancreatic cancer are poor as curative approaches are only available to the minority of patients who have localized tumors for which surgery may be an option. The past decade has established fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) as the new standard of care following resection for fit patients with resectable pancreatic tumors.

Emerging Treatment Strategies in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of cancer death in well-developed countries. Therapeutic advances in PDAC to date have been modest. Recent progress to understand the molecular landscape of the disease has opened new treatment opportunities for a small subset of patients, frequently those with KRAS wild-type disease.

Survival Outcomes Based on Sequence of Therapy Using FOLFIRINOX and Nab-Paclitaxel + Gemcitabine in Metastatic Pancreatic Ductal Adenocarcinoma.

Objectives: Optimal sequence of therapy for patients with metastatic pancreatic ductal adenocarcinoma is unknown. Combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and nab-paclitaxel + gemcitabine (nab-p/gem) are standard first-line (1L) therapies. They have never been prospectively compared.

Clinical Activity of Selitrectinib in a Patient With Mammary Analogue Secretory Carcinoma of the Parotid Gland With Secondary Resistance to Entrectinib.

NTRK gene fusions are found in <1% of all cancers but are uniformly present in mammary analog secretory carcinomas (MASC) of the salivary glands. Two selective histology-agnostic tropomyosin receptor kinase (TRK) inhibitors are currently approved for malignancies with these oncogenic fusions. Resistance to TRK inhibition has been recognized, and the mediating mechanisms are presently being studied.

From state-of-the-art treatments to novel therapies for advanced-stage pancreatic cancer.

Improvements in the outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) have lagged behind advances made in the treatment of many other malignancies over the past few decades. For most patients with PDAC, cytotoxic chemotherapy remains the mainstay of treatment. For patients with resectable disease, modified 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (mFOLFIRINOX) is the standard-of-care adjuvant therapy, although data from several randomized trials have shown improved outcomes with neoadjuvant treatment strategies.

Survival of patients with metastatic HER2 positive gastro-oesophageal cancer treated with second-line chemotherapy plus trastuzumab or ramucirumab after progression on front-line chemotherapy plus trastuzumab.

Background: The role of continuing anti-HER2 therapy beyond progression on front-line therapy in patients with metastatic HER2 positive gastro-oesophageal cancer (GEC) is unclear. Continued chemotherapy plus trastuzumab (CT) has never been compared with the current standard second-line treatment, chemotherapy plus ramucirumab (CR).

Methods: The Flatiron Health electronic health record derived database, a nationwide database comprising patient-level structured and unstructured data, curated via technology-enabled abstraction, was reviewed for patients with metastatic HER2 positive GEC who received first-line CT, followed by second-line CT or CR.

Benefit of adjuvant chemotherapy based on lymph node involvement for oesophageal cancer following trimodality therapy.

Background: Oesophageal cancer (OC) survival rates have improved since the widespread adoption of neoadjuvant chemoradiation therapy (NACRT) followed by oesophagectomy (trimodality therapy). Unfortunately, the overall prognosis for patients with locally advanced disease remains poor. In this study, we sought to assess the effect of adjuvant chemotherapy (AC) in patients treated with trimodality therapy.

Placenta-based therapies for the treatment of epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering skin disease caused by mutations in the COL7A1 gene. These mutations lead to decreased or absent levels of collagen VII at the dermal-epidermal junction. Over the past decade, significant progress has been made in the treatment of RDEB, including the use of hematopoietic cell transplantation, but a cure has been elusive.