Oncologist最新文献

We present a 54-year-old White male with a diagnosis of stage IV pancreatic neuroendocrine carcinoma. Next-generation sequencing of the tumor/blood identified a complex tumor genome, which included a rearranged during transfection (RET) gene fusion. The patient initially received cytotoxic chemotherapy with a significant radiographic response. After 4 cycles of chemotherapy, the patient was transitioned to a clinical trial using selpercatinib, a RET inhibitor, as maintenance therapy. Unfortunately, our patient developed progression of disease at the first treatment monitoring scan. Our patient suffered primary resistance to RET-targeted therapy. Proposed mechanisms of resistance include intrinsic resistance of the nuclear receptor co-activator 4-RET fusion to RET inhibition, the RET fusion representing a passenger alteration to another tumorigenic driver pathway and/or decreased efficacy of RET inhibition after platinum-based chemotherapy. Our patient's clinical course highlights the fact that "actionable" genomic alterations do not always equate to patient benefit.

Background: Peritoneal metastasis (PM) after the rupture of hepatocellular carcinoma (HCC) is a critical issue that negatively affects patient prognosis. Machine learning models have shown great potential in predicting clinical outcomes; however, the optimal model for this specific problem remains unclear.

Methods: Clinical data were collected and analyzed from 522 patients with ruptured HCC who underwent surgery at 7 different medical centers. Patients were assigned to the training, validation, and test groups in a random manner, with a distribution ratio of 7:1.5:1.5. Overall, 78 (14.9%) patients experienced postoperative PM. Five different types of models, including logistic regression, support vector machines, classification trees, random forests, and deep learning (DL) models, were trained using these data and evaluated based on their receiver operating characteristic curve and area under the curve (AUC) values and F1 scores.

Results: The DL models achieved the highest AUC values (10-fold training cohort: 0.943, validation set: 0.928, and test set: 0.892) and F1 scores (10-fold training set: 0.917, validation cohort: 0.908, and test set:0.899) The results of the analysis indicate that tumor size, timing of hepatectomy, alpha-fetoprotein levels, and microvascular invasion are the most important predictive factors closely associated with the incidence of postoperative PM.

Conclusion: The DL model outperformed all other machine learning models in predicting postoperative PM after the rupture of HCC based on clinical data. This model provides valuable information for clinicians to formulate individualized treatment plans that can improve patient outcomes.

The prognosis of patients with glioblastoma (GBM) remains poor despite current treatments. Targeted therapy in GBM has been the subject of intense investigation but has not been successful in clinical trials. The reasons for the failure of targeted therapy in GBM are multifold and include a lack of patient selection in trials, the failure to identify driver mutations, and poor blood-brain barrier penetration of investigational drugs. Here, we describe a case of a durable complete response in a newly diagnosed patient with GBM with leptomeningeal dissemination and PTPRZ1-MET fusion who was treated with tepotinib, a brain-penetrant MET inhibitor. This case of successful targeted therapy in a patient with GBM demonstrates that early molecular testing, identification of driver molecular alterations, and treatment with brain-penetrant small molecule inhibitors have the potential to change the outcome in select patients with GBM.

Background: Patients with metastatic renal cell carcinoma (mRCC) experience emotional distress and limited supportive care access. This study assesses a mindfulness app's feasibility, acceptability, and preliminary efficacy in improving emotional symptoms, trait mindfulness, and overall quality of life for patients with mRCC on immunotherapy.

Methods: This multinational study recruited patients with mRCC undergoing immunotherapy from Brazil and the United States. Participants were required to engage in mindfulness app-based activities for 20-30 min daily, at least 4 days per week, over a 4-week period. Assessments were conducted at weeks 0, 2, 4, and 12 to evaluate emotional symptoms (PROMIS-Anxiety and Depression, Fear of Cancer Recurrence-7), fatigue (Brief Fatigue Inventory), trait mindfulness (Mindfulness Attention Awareness Scale), and quality of life (Functional Assessment of Chronic Illness Therapy-General). Self-reported data were used to assess adherence. Linear mixed-effects models were used to evaluate changes over time for the measured outcomes.

Results: Among 50 patients with mRCC, the feasibility of this intervention was demonstrated; 96% of patients were assessed at week 4, with high adherence rates reported by 75% of patients. Participants expressed positive feedback on the smartphone-based approach. Significant improvements were observed in emotional symptoms, fatigue, and quality of life scores from baseline to post-intervention (P = .001 for each), suggesting the positive impact of this intervention.

Conclusion: Our findings provide encouraging evidence for the feasibility and acceptability of a mindfulness app-based intervention among patients with mRCC. This intervention may offer a viable and accessible means of providing psychosocial support to patients with mRCC.

Background: Pemigatinib demonstrated efficacy in fibroblast growth factor receptor (FGFR)-altered cholangiocarcinoma (CCA) in the FIGHT-202 trial. However, limited real-world evidence exists on treatment patterns and outcomes in this setting.

Patients and methods: Patient characteristics, treatment patterns, and outcomes of US adults who received pemigatinib for unresectable, locally advanced or metastatic CCA were collected via retrospective physician-abstracted chart review. Results were summarized using descriptive statistics.

Results: Data from 120 patients (49.2% male; 55.0% White; 19.2% Hispanic; median age at initial pemigatinib prescription, 64.5 years) were collected from 18 physicians/practices. At the time of prescribing, 90.0% of patients had metastatic disease. FGFR2 testing was completed for 92.5% of patients; of those, all but one (result unknown) tested positive, and 95.5% were tested using next-generation sequencing. Pemigatinib was prescribed as second- and third-line therapy among 94.2% and 5.8% of patients, respectively. The most common starting dosage was 13.5 mg daily for 14 days of 21-day cycles (87.5% of patients). Among 60 patients (50.0% of the full cohort) who discontinued pemigatinib during the 6.5-month median study follow-up period, 68.3% discontinued due to disease progression. The median real-world progression-free survival (rwPFS) from the date of pemigatinib initiation was 7.4 months (95% CI: 6.4-8.6), and the real-world overall response rate (rwORR) was 59.2% (95% CI: 50.0%-68.4%).

Conclusion: This study complements the FIGHT-202 clinical trial by assessing the use of pemigatinib among a diverse population of patients with CCA under real-world conditions. Findings support the clinical benefit of pemigatinib demonstrated in FIGHT-202.

Background: Both novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) and pertuzumab and trastuzumab (HP) combined with chemotherapy(C) regimens are the choice of treatment for HER2 positive metastatic breast cancer (MBC) after tyrosine kinase inhibitors (TKIs). Our team's previous research has shown significant therapeutic effects of novel anti-HER2 ADCs in patients with TKIs treatment failure. Unfortunately, there is currently no data available to compare novel anti-HER2 ADCs with HP combined with chemotherapy regimens. This study was conducted to compare the efficacy and safety of novel anti-HER2 ADCs with that of the HP combined with chemotherapy regimen in patients for whom TKI treatment failed.

Materials and methods: HER2-positive MBC who used novel anti-HER2 ADCs and HP combined with a chemotherapy regimen from January 2019 to August 2023 were included, and all patients received TKIs. The primary study endpoint was progression-free survival (PFS), while the secondary study endpoints were objective response rate (ORR), clinical benefit rate (CBR), and safety.

Results: A total of 150 patients, of which 83 are in the novel anti-HER2 ADCs group and 67 are in the HP combined with chemotherapy. Among these novel anti-HER2 ADCs, 36 patients received treatment with trastuzumab deruxtecan (T-Dxd), and 47 patients received treatment with other new types of ADCs. The median PFS of the novel anti-HER2 ADCs group and HP combined with the chemotherapy group were 7.0 months and 8.9 months, respectively, with ORR of 51.8% and 26.9%, and CBR of 69.9% and 65.7%, respectively. In subgroup, patients receiving T-Dxd showed improvement in PFS compared to the HP combined with chemotherapy group. The most common grade 3-4 adverse events in the novel anti-HER2 ADCs group and the HP combined with chemotherapy group were neutropenia and gastrointestinal symptoms.

Conclusions: In HER2-positive MBC for whom TKI treatment has failed, novel anti-HER2 ADCs and the HP combined with chemotherapy regimen both showed moderate efficacy and tolerable toxicity. Novel anti-HER2 ADCs are the preferred treatment recommendation for TKI failure patients. Meanwhile, based on the results of this study, the HP combined with chemotherapy regimen may also be an option, especially for patients with low accessibility.

Cancer manifests through a spectrum of mutations, including gene fusions termed oncofusions. These structural alterations influence tumorigenesis across various cancer types. Oncofusions arise primarily from genomic rearrangements and operate through deregulation or hybrid gene formation mechanisms. Notable examples such as BCR::ABL and EWS::FLI1 underscore their clinical significance. Several case studies exemplify the role of identifying and targeting oncofusions in guiding treatment decisions and improving patient outcomes. However, challenges persist in discerning drivers from passenger mutations and addressing acquired resistance. Despite advancements, the complexity of oncofusions warrants further exploration of their full potential as therapeutic targets, requiring a multidisciplinary approach integrating genomics, functional studies, and innovative drug discovery strategies to achieve precision in medicine.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0. Adverse events were deemed sotorasib-related per investigator causality assessment.

Results: In the pooled population (n = 549), TRAEs were reported in 388 (70.7%) patients (grade 1: 124 [22.6%]; grade 2: 117 [21.3%]; grade ≥ 3: 147 [26.8%]). Gastrointestinal and hepatic TRAEs, including diarrhea (171 [31.1%]), nausea (80 [14.6%]), elevated alanine aminotransferase (ALT; 68 [12.4%]), and elevated aspartate aminotransferase (AST; 67 [12.2%]) were the most common (≥10%). Dose interruption and dose reduction of sotorasib resulted in the resolution of >90% of diarrhea events; median time to resolution were 18.0 days and 22.0 days, respectively. Similar trends were observed for elevated ALT and AST events. Patients who stopped immunotherapy <3 months before initiating sotorasib had a higher incidence of treatment-related hepatotoxicity (80/240 [33.3%]) than those who stopped immunotherapy ≥3 months before initiating sotorasib (26/188 [13.8%]). Treatment-related pneumonitis/interstitial lung disease (ILD) and corrected QT (QTc) prolongation were observed in 9 (1.6%) and 4 (0.7%) patients, respectively. Two (0.4%) patients died with TRAEs, 1 with ILD whose ultimate cause of death was disease progression, and the other with an unknown cause.

Conclusions: Sotorasib has a well-characterized safety profile in patients with KRAS G12C-mutated advanced NSCLC, and key risks are manageable with dose modification.