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. METHODS: A nationwide deidentified electronic health record-derived database was reviewed for patients diagnosed with mCRC between 2015 and 2020. Patients who received at least 2 lines of standard systemic therapy followed by treatment with either TAS-102 or regorafenib were included for analysis. Kaplan-Meier and propensity score-weighted proportional hazards models were used to compare survival outcomes between groups. RESULTS: The records of 22,078 patients with mCRC were reviewed. Of these, 1,937 patients received at least 2 lines of standard therapy followed by regorafenib and/or TAS-102. Median OS for the TAS-102 alone or prior regorafenib group (n=1,016) was 6.66 months (95% CI, 6.16-7.18 months) compared with 6.30 months (95% CI, 5.80-6.79 months) for regorafenib alone or prior to TAS-102 (n=921; P=.36). A propensity score-weighted analysis controlling for potential confounders did not demonstrate a significant difference in survival between groups (hazard ratio, 0.99; 95% CI, 0.90-1.09; P=.82). A subgroup analysis did not identify any significant differences in outcomes regarding age, performance status, tumor sidedness, microsatellite instability status, or RAS/RAF status. CONCLUSIONS: This analysis of real-world data found that OS was similar for patients with mCRC who were treated with TAS-102 compared with regorafenib. Median OS with both agents in a real-world setting was similar to that shown in the clinical trials that led to their approvals. A prospective trial comparing TAS-102 and regorafenib would unlikely change current management of patients with refractory mCRC.

Durable response to BRAF inhibitor monotherapy in recurrent metastatic low grade serous ovarian cancer.

Low grade serous ovarian cancers (LGSOC) in an advanced setting have limited systemic treatment options. In this paper we report a case of metastatic LGSOC harboring a BRAF mutation, treated with dabrafenib. We discuss the clinical, pathologic and molecular characteristics as well as surgical considerations and ongoing investigations in LGSOC.

Real-world comparison of survival outcomes with cisplatin versus carboplatin in patients with limited-stage small-cell lung cancer.

INTRODUCTION: Limited-stage small-cell lung cancer (LS-SCLC) is potentially curable with concurrent chemoradiation (CRT). Cisplatin is the preferred platinum for the chemotherapy backbone in national guidelines. Unfortunately, many LS-SCLC patients are elderly, with comorbidities and poor performance status (PS), which preclude the use of cisplatin. Carboplatin may be a suitable alternative. This analysis evaluates the overall survival (OS) and time to next treatment (TTNT) in LS-SCLC patients receiving concurrent CRT by platinum use. MATERIALS AND METHODS: The study included LS-SCLC patients in the Flatiron Health nationwide de-identified electronic health record-derived database who received CRT in 2013-2019 with follow-up through May 2020. TTNT and OS were compared using both unadjusted and inverse propensity-weighted Cox proportional hazards models. RESULTS: This study included patients treated with carboplatin (n = 600) or cisplatin (n = 572) in combination with etoposide and radiation. Cisplatin patients were younger, had a shorter time from diagnosis to radiation, and had less kidney disease. In an unadjusted analysis, median overall survival (mOS) was greater in the cisplatin group than the carboplatin group with mOS of 22.3 months vs. 19.2 months and Hazard Ratio (HR) of 0.83 (p = 0.01). In the inverse propensity-weighted analysis, this difference was no longer significant (HR 0.93, p = 0.37). No differences were seen in TTNT. CONCLUSION: When balancing on key clinical factors, we observed no statistical difference in OS or TTNT by platinum choice in real-world LS-SCLC patients treated with CRT.  Although observational, the results from this large data set are consistent with the hypothesis that either cisplatin or carboplatin is an appropriate therapy regardless of health status.

Durable response to first-line PARP inhibition in BRCA-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; BRCA1/2 mutations are identified in up to 5% of CCA patients and may be an additional target for novel treatment approaches. While BRCA mutations have been shown in clinical trials to predict response to poly(ADP-ribose) polymerase (PARP) inhibitors in several solid tumors including breast, ovarian, prostate, and pancreas, no similar large-scale trials have been published in CCA to date. We report here a durable response to PARP inhibitor monotherapy in BRCA-mutated extrahepatic CCA; to our knowledge, this is the second report of first-line PARP inhibitor monotherapy and the first reported use of the second-generation PARP inhibitor talazoparib in this setting. Case Description: We report the case of a 79-year-old man with metastatic extrahepatic CCA harboring a somatic BRCA1 mutation who declined chemotherapy and was instead treated in the first-line metastatic setting with the PARP inhibitor talazoparib; he experienced a complete radiographic response six months into treatment and has remained on talazoparib for over three years without evidence of disease recurrence. Conclusions: This case adds to a growing list of retrospective studies supporting the clinical activity of PARP inhibitors in BRCA-mutated extrahepatic CCA. However, prospective data are clearly needed prior to adoption of this strategy in clinical practice. Fortunately, multiple trials investigating novel combination therapies utilizing PARP inhibitors in CCA are underway.

Case report: Adenosquamous carcinoma of the prostate with greater than 20 month response to multimodal therapy.

Adenosquamous carcinoma is an extremely rare and lethal subtype of prostate cancer affecting an estimated 0.03 per million men annually. It has been associated with prior hormone therapy for prostate adenocarcinoma. We present a case of de novo adenosquamous carcinoma of the prostate treated with a multimodal approach including surgery, androgen-deprivation therapy, chemotherapy, and radiation.

Intracranial bleeding following soccer-related head trauma in a young student with occult factor VII deficiency.

It is important to obtain coagulation tests to assess bleeding risk in trauma patients undergoing emergency surgery when a bleeding disorder may be obscured. Identifying specific clotting factor defects is critical in successful patient management.

Cerebral Sinus Venous Thrombosis in the Setting of Acute Mastoiditis.

Cerebral sinus venous thrombosis (CSVT) is a rare complication of acute mastoiditis with a declining incidence in the post-antibiotic era. In the adult population its incidence ranges from three to four cases per million. Here we present a case of a 47-year-old female with triple negative breast cancer on chemotherapy who underwent a molar tooth extraction, which was followed two weeks later by the sudden onset of left-sided frontotemporal headache radiating down the face, left ear fullness with associated hearing loss, toothache, and left orbital pain. Imaging studies performed included magnetic resonance imaging (MRI) as well as magnetic resonance venography (MRV), both of which showed thrombosis of the left transverse sinus, sigmoid sinus as well as the internal jugular vein, which was consistent with a diagnosis of cerebral sinus venous thrombosis. Following the diagnosis, the patient was managed with anti-coagulation and antibiotics, which resulted in improvement of her symptoms. This case highlights the need to be vigilant in patients with acute mastoiditis for the above clinical syndrome in order to promptly diagnose this rare complication and avoid life-threatening consequences.

Hyperprogression in PDL1 Expressive, Recurrent Gastroesophageal-junction Adenocarcinoma After Pembrolizumab.

Hyperprogression is a pattern of accelerated tumor growth noted uncommonly after the use of immune checkpoint inhibitors in some patients. We present a 56-year-old female with gastroesophageal junction (GEJ) adenocarcinoma who was initially treated with neoadjuvant radiation and chemotherapy with carboplatin and paclitaxel, followed by esophagogastrectomy and postoperative FOLFOX chemotherapy. After a stable two-year course, she was noted to have recurrence at the GEJ which was biopsy confirmed. She was started on pembrolizumab, after which she developed several new metastases noted on the PET/CT. Lesions were noted in iliac bones, spine, retroperitoneal lymph nodes, hilar nodes, mediastinum, and lungs. Postdiscontinuation of the pembrolizumab, she received six cycles of paclitaxel with ramucirumab and showed remarkable improvement on the next imaging scan with resolution of osseous lesions, lung nodules and significant improvement in hilar, mediastinal, and retroperitoneal lymph nodes. We hope that this case report sheds further light on this uncommon complication of immune checkpoint inhibitors.

Aseptic Meningitis as an Immune-Related Adverse Event after Pembrolizumab.

INTRODUCTION: The management of patients with advanced malignancies is challenging, although recent advances with immunotherapy have shown better outcomes. Pembrolizumab has been associated with a variety of immune-related side effects, but the occurrence of aseptic meningitis is rare. CASE: A 55-year-old male with a history of metastatic lung adenocarcinoma previously treated with pembrolizumab presented with persistent severe headaches and photophobia. Subsequent workup with cerebrospinal fluid analysis showed elevated opening pressure, increased nucleated cells with 30% lymphocytes, elevated protein levels, and normal glucose levels. The patient was started on high doses of IV steroids and progressed with significant improvement of his symptoms. DISCUSSION: Given the rarity of this side effect, this case is a reminder that immune checkpoint inhibitors can cause aseptic meningitis and its early recognition is important for initiation of therapy with steroids and prompt discontinuation of the immunotherapy agent.