The role of PARP inhibitors in germline BRCA-associated pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that remains a challenge to treat. In pursuit of personalized medicine, researchers continue active exploration of the genetic and molecular framework of PDAC to apply novel therapeutics and enhance outcomes. In patients who have PDAC, germline mutations-such as those in the BRCA1/2 and PALB2 genes-are predominantly associated with the DNA damage response and repair pathway. On the basis of studies completed in patients with BRCA-mutated advanced breast and ovarian cancer, the poly(ADP-ribose) polymerase (PARP) inhibitors have been evaluated for safety, tolerability, and efficacy in patients with advanced PDAC who are carrying germline BRCA gene mutations. Results have demonstrated meaningful activity and identified BRCA as a predictive and targetable biomarker in PDAC, and have also identified the role of olaparib as a maintenance therapy in PDAC. On the basis of the principle of synthetic lethality, and to avert resistance to PARP inhibitors, clinical trials of combination therapy with PARP inhibitors and platinum-based chemotherapy have been conducted with an early signal. As we continue to explore the role of PARP inhibitors in the management of PDAC, recent clinical trials are studying the effectiveness of PARP inhibitors in combination with immunotherapy, targeted inhibitors, and angiogenesis inhibitors. The next steps are to understand the role of PARP inhibitors beyond germline BRCA in other homologous recombination repair gene mutations and in other subgroups of patients with PDAC.

Pancreatic cancer-A disease in need: Optimizing and integrating supportive care.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that continues to be challenging to treat. PDAC has the lowest 5-year relative survival rate compared with all other solid tumor malignancies and is expected to become the second-leading cause of cancer-related death in the United States by 2030. Given the high mortality, there is an increasing role for concurrent anticancer and supportive care in the management of patients with PDAC with the aims of maximizing length of life, quality of life, and symptom control. Emerging trends in supportive care that can be integrated into the clinical management of patients with PDAC include standardized supportive care screening, early integration of supportive care into routine cancer care, early implementation of outpatient-based advance care planning, and utilization of electronic patient-reported outcomes for improved symptom management and quality of life. The most common symptoms experienced are nausea, constipation, weight loss, diarrhea, anorexia, and abdominal and back pain. This review article includes current supportive management strategies for these and others. Common disease-related complications include biliary and duodenal obstruction requiring endoscopic procedures and venous thromboembolic events. Patients with PDAC continue to have a poor prognosis. Systemic therapy options are able to palliate the high symptom burden but have a modest impact on overall survival. Early integration of supportive care can lead to improved outcomes.

Real-World Outcomes of Atezolizumab with Bevacizumab Treatment in Hepatocellular Carcinoma Patients: Effectiveness, Esophagogastroduodenoscopy Utilization and Bleeding Complications.

The IMbrave150 trial established atezolizumab with bevacizumab (A+B) as standard care for hepatocellular carcinoma (HCC), recommending an esophagogastroduodenoscopy (EGD) within 6 months of treatment initiation to prevent bleeding from esophagogastric varices. The necessity of mandatory EGD for all patients remains unclear. We retrospectively analyzed 112 HCC patients treated with A+B at five Canadian cancer centers from 1 July 2020 to 31 August 2022. A+B was the first-line therapy for 90% of patients, with median overall survival at 20.3 months and progression-free survival at 9.6 months. There was no survival difference between patients with bleeding and those without. Before A+B, 71% (n = 79) of patients underwent an EGD within 6 months, revealing varices in 41% (n = 32) and requiring intervention in 19% (n = 15). The overall bleeding rate was 15% (n = 17), with GI-specific bleeding occurring in 5% (n = 17). In the EGD group, GI-specific bleeding was 6% (n = 5) while in the non-EGD group, it was 3% (n = 1). Non-GI bleeding was observed in 10% (n = 11) of patients. Outcomes for HCC patients treated with A+B in Canada were comparable to IMbrave150. There was no increase in GI bleeding in patients without pre-treatment EGD, possibly supporting a selective EGD approach.

Venous thromboembolism events in patients with advanced cancer on immune checkpoint inhibitors.

Aim: To evaluate the correlation between venous thromboembolism events (VTEs) and immune checkpoint inhibitor (ICI)-based regimens. Methods: This is a retrospective study of 403 patients with advanced cancer on ICI-based regimens. Results: We report 8% VTE incidence post-ICI initiation over a median of 11.1 months of follow-up. Compared with single-agent ICI, dual-ICI was significantly correlated with higher incidence of VTE (odds ratio [OR]: 4.196, 95% CI: 1.527-11.529, p = 0.005), but chemotherapy-immuno-oncology combination was not (OR: 1.374, 95% CI: 0.285-6.632, p = 0.693). Subsequent systemic therapy post-ICI was also independently associated with higher VTE incidence (OR: 2.599, 95% CI: 1.169-5.777, p = 0.019). Conclusion: Our findings suggest potential underreporting of VTE incidence in ICI clinical trials. As dual-ICI is becoming more prevalent in cancer management, clinicians should maintain vigilance regarding VTE in patients with advanced cancer on ICI-based regimens.

Safety and Clinical Outcomes of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Diseases.

Immunotherapy has revolutionized treatment outcomes in numerous cancers. However, clinical trials have largely excluded patients with autoimmune diseases (ADs) due to the risk of AD flares or predilection for developing organ-specific inflammation. The objective of this study was to evaluate the safety and efficacy of immunotherapy in patients with cancer and preexisting ADs. A retrospective, single-center study of patients with cancer initiated on immune checkpoint inhibitors between 2012 and 2019 was conducted. The primary outcome was the development of immune-related adverse events (irAEs) with respect to the presence of AD at baseline. Associations were assessed using Kaplan-Meier curves, bivariate and multivariable analyses. Of the 417 patients included in this study, 63 patients (15%) had preexisting ADs. A total of 218 patients (53%) developed at least 1 irAE. There was no association between the presence of baseline AD on the development, grade, or number of irAEs; time to irAE or irAE recovery; systemic corticosteroid or additional immunosuppressant treatment for irAEs; permanent treatment discontinuation; or overall response rate. Two smaller cohorts were studied, melanoma and non-small cell lung cancer, and there was no effect of baseline AD on overall survival on either cohort. However, a greater proportion of patients with baseline ADs had full recovery from their irAE (P=0.037). Furthermore, age below 65, baseline steroid use, and single-agent immunotherapy regimens were protective in terms of the development of irAEs. Our study suggests that immune checkpoint inhibitors have similar safety and efficacy profiles in patients with preexisting ADs.