DANA-FARBER CANCER INSTITUTE

The TiNivo-2 trial, reported in The Lancet by Choueiri et al., found that immune checkpoint inhibitor rechallenge with nivolumab plus tivozanib did not improve progression-free survival compared to tivozanib alone in metastatic renal cell carcinoma patients post-immune checkpoint inhibitor treatment. Median progression-free survival was 5.7 months vs 7.4 months, with no significant difference. The study suggests that immune checkpoint inhibitor rechallenge should be discouraged and that tivozanib monotherapy is effective in this setting.

August 2024 biopharma deals highlight trends in bispecific T-cell engagers, CD-19 targeting in autoimmune diseases, and Chinese biopharma innovation. Merck's $1.3B acquisition of Curon's CD3xCD19 BiTE CN201 reflects confidence in early trial outcomes and market enthusiasm for BiTEs. JPMorgan reports a 50% reduction in upfront payments since 2020, indicating a more back-loaded deal structure.

Dana-Farber Cancer Institute raised $2.5 billion in a seven-year campaign, supporting clinical trials, patient care equity, new facilities, and early cancer detection. The campaign, led by Dr. Laurie Glimcher, received over 2.2 million gifts from 900,000 donors globally, with the Pan-Mass Challenge contributing $425 million. The funds have enabled significant advancements in cancer research and care.

Immunotherapies are crucial for multiple myeloma (MM) but face resistance and relapse. Proteasome inhibitors (PIs) and targeted therapies like BCL2 and BRAF/MEK inhibitors offer alternatives. Clonal evolution and subclonal mutations drive disease progression. Combination therapies, including melphalan, increase mutational load. Resistance to lenalidomide and anti-CD38 antibodies is common, but combinations like carfilzomib, daratumumab, and dexamethasone improve progression-free survival (PFS). BCMA-targeted antibody-drug conjugates (ADCs) show promise. Targeted inhibitors for BCL2, BRAF/MEK, and NSD2 benefit refractory patients. Despite clinical promise, access to these therapies is limited, highlighting the need for cost-effective treatments and innovative approaches.

Oncology nurses should discuss anti-emetics, hair loss, and interstitial lung disease with patients before starting trastuzumab deruxtecan (T-DXd). The DESTINYBreast-12 trial showed T-DXd's promising response rates and progression-free survival in HER2-positive metastatic breast cancer, including with brain metastases. However, T-DXd can cause nausea/vomiting, hair loss, and interstitial lung disease, with symptoms like shortness of breath and cough requiring early management.

The CABINET trial showed cabozantinib significantly improved progression-free survival in previously treated patients with advanced extrapancreatic or pancreatic neuroendocrine tumors compared to placebo. Adverse events were consistent with cabozantinib's known safety profile, supporting its use as a new treatment option.

Breast cancer experts discuss key studies from the 2024 ESMO Congress, including a phase 2 trial with nivolumab and ipilimumab in TNBC, a real-world registry trial on stage I TNBC, a neoadjuvant study showing high survival rates in non-CR patients, and research on PD-L1 expression in metastatic TNBC and ER-low tumors. Additionally, endocrine therapy impacts in premenopausal ER-positive breast cancer patients were highlighted.

The FDA’s Oncologic Drug Advisory Committee (ODAC) voted 11 to 1 against the use of checkpoint inhibitors (CPIs) in patients with metastatic or unresectable esophageal squamous cell carcinoma with PD-L1 expression less than 1, citing unfavorable risk-benefit assessment. The discussion focused on data from trials supporting the approvals of nivolumab, pembrolizumab, and tislelizumab, which showed marginal or unfavorable outcomes in patients with PD-L1 expression under 1, with higher benefits observed in those with expression over 1. The notable risks of CPIs, including immune-mediated adverse effects, were also highlighted.

Dana-Farber Cancer Institute launches IGNITE, the first national pediatric hematology-oncology health equity research consortium, aiming to address disparities in cancer outcomes for children from low-income households and marginalized communities by developing and evaluating health equity interventions.

Experts at the International Myeloma Society 21st Annual Meeting discuss the progression from MGUS and SMM to MM, highlighting the importance of early intervention in high-risk SMM patients using treatments like lenalidomide and dexamethasone to reduce progression risk.