Articles related to IMMUNOTHERAPY

Discover how to navigate the evolving therapeutic landscape for advanced melanoma, with a focus on the latest immunotherapies, mitigation of treatment-associated adverse events, and patient-centric strategies to enhance shared decision-making and quality of life.

Permissive cardiotoxicity strategy could enhance trastuzumab treatment outcomes in HER2-positive breast cancer patients, despite requiring more research into its long-term safety. A study conducted at McMaster University and published in The Oncologist explored the feasibility of a permissive cardiotoxicity strategy in patients with HER2-positive breast cancer undergoing trastuzumab treatment. Although trastuzumab significantly improves outcomes in these patients, up to 4% of them may experience cardiac dose-limiting toxicity (cDLT), resulting in therapy discontinuation, which can negatively impact patient outcomes. The researchers employed a retrospective cohort study of 51 patients who had been referred to the cardio-oncology service between January 2016 and May 2021 for left ventricular dysfunction after trastuzumab administration. Notably, a permissive cardiotoxicity strategy was applied, which allows the continuation of trastuzumab therapy while closely monitoring mild to moderate cardiotoxicity. The primary outcomes for this study were left ventricular (LV) function and completion of an entire course of trastuzumab. Astonishingly, 92% of patients (47 out of 51) were able to complete their full course of HER2-targeted therapy without experiencing cDLT. However, 6% developed cDLT during trastuzumab treatment, and even after discontinuation, they were more likely to experience persistent cardiotoxicity. Interestingly, despite most patients regaining their LV function post-treatment, 14% persisted […]

Dr. Vanita Noronha from the Tata Memorial Centre in Mumbai emphasizes the need for rethinking drug dosing approaches for modern therapies like nivolumab, an immunotherapy. Ongoing and planned trials in India are exploring cost-effective alternative dosing regimens due to the prohibitive cost of standard-dose therapies. Dr. Vanita Noronha from the Tata Memorial Centre highlighted the role of factors such as pharmacokinetics, pharmacodynamics, receptor affinity, and drug elimination in determining drug dosing during a Q&A session with Clinical Advances in Hematology & Oncology. The traditional dosing approach does not apply to modern therapies like nivolumab, an immunotherapy that binds to the PD-1 protein. According to Dr. Noronha, the drug reaches receptor saturation at a low dose, and hence increasing dosage does not increase receptor binding. For nivolumab to be effective, 70-75% of the PD-1 receptor needs to be occupied, which occurs at a dose of 0.3 mg/kg, only a tenth of the usually administered dose of 3 mg/kg. Dr. Noronha further described a study published in the Journal of Clinical Oncology in 2023 on low-dose nivolumab in head and neck cancer. The study, conducted with Indian patients who cannot afford standard dosing, used a regimen of oral metronomic chemotherapy along with […]

Demonstrating compelling efficacy in the EV-103 trial, the combination of enfortumab vedotin-ejfv and pembrolizumab emerges as a promising treatment for patients with locally advanced or metastatic urothelial carcinoma ineligible for cisplatin-based chemotherapy. The recent approval of enfortumab vedotin-ejfv in combination with pembrolizumab for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who are ineligible for cisplatin-based chemotherapy was substantiated by compelling results from the multi-cohort Phase 1b/2 EV-103 trial. In the dose escalation cohort and cohort A of the trial, patients received this innovative combination therapy. In cohort K, patients were randomized to receive either the combination or enfortumab vedotin-ejfv monotherapy. The main efficacy outcome measures were the objective response rate (ORR) and duration of response (DOR), with the ORR reaching 68% (95% CI, 58.7-76.0) among the 121 patients who received the combination therapy. Moreover, the median DOR was reported as 22.1 months for the dose escalation and cohort A. Nevertheless, patients did report a range of adverse reactions, most commonly increased glucose, increased aspartate aminotransferase, rash, and decreased hemoglobin, among others. The approval of this therapy is dependent on the validation and depiction of clinical benefits from the ongoing Phase 3 EV-302 confirmatory trial. Given the promising ORR […]

This study presents findings from a Phase I clinical trial examining the use of Stereotactic Body Radiotherapy (SBRT) combined with pembrolizumab (P) in treating advanced solid tumors, with a focus on the safety and effectiveness of partial tumor irradiation. The trial involved 97 patients, 47% of whom received at least one partial radiation treatment. The overall one-year local failure (LF) rate was 7.6%, and the results suggest an association between tumor response to SBRT+P and improved overall survival (OS), particularly for irradiated tumors. The trial also explored the role of biomarkers, finding that a high Radiomics Score (RS), based largely on CD8+ T cell levels, was linked to better LF, progression-free survival (PFS), and OS. Conversely, increased levels of circulating cytokine IL-8 were associated with worse PFS and OS. The study concluded that SBRT+P is safe for patients with large, advanced solid tumors and recommended further research to compare the effectiveness of complete versus partial tumor irradiation in the context of immunotherapy.

In the phase III GAIA–CLL13 study, researchers investigated time-limited treatment options for fit patients with chronic lymphocytic leukemia (CLL) and a low burden of coexisting conditions. The study compared the efficacy of chemoimmunotherapy with venetoclax-obinutuzumab, both with and without ibrutinib. The results showed that the venetoclax-based regimens were superior to chemoimmunotherapy in terms of achieving undetectable minimal residual disease and longer progression-free survival (PFS). The percentages of patients with undetectable minimal residual disease were remarkably high, with 86.5% in the venetoclax-obinutuzumab group and 92.2% in the venetoclax-obinutuzumab-ibrutinib group, among the highest reported in first-line treatment for CLL. The study confirmed the significant prognostic value of undetectable minimal residual disease at the end of time-limited treatment, as it translated into superior PFS. The study emphasized the need for treatment options for fit CLL patients with normal renal function, as data from prospective, randomized clinical studies evaluating the safety and efficacy of venetoclax-obinutuzumab in this specific patient population were lacking. The study demonstrated that the venetoclax-obinutuzumab-ibrutinib combination had a higher incidence of tumor lysis syndrome compared to venetoclax-ibrutinib, likely due to the simultaneous administration of obinutuzumab with ibrutinib, leading to rapid depletion of CLL cells. The findings highlight the importance of continuing […]