Non-clear cell renal cell carcinoma (nccRCC) comprises a highly heterogeneous group of distinct histological and molecularly defined entities. Because of this biological diversity, prognosis and treatment response vary widely, and outcomes in advanced disease remain poor. Contemporary workups necessitate an integration of morphology, immunohistochemistry, molecular diagnostics, and hereditary syndrome screening to guide optimal clinical choices. Historically, single-agent vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) were established as the frontline treatment standard over mTOR inhibitors. However, current practice has pivoted toward histology-specific strategies and immune checkpoint inhibitor (ICI) combination backbones. For advanced papillary RCC, cabozantinib monotherapy or IO-TKI combinations such as lenvatinib-pembrolizumab are preferred frontline strategies. Conversely, chromophobe RCC shows diminished responses to immunotherapy, leaving lenvatinib-everolimus or lenvatinib-pembrolizumab as the most valid prospective options. Highly aggressive variants such as collecting duct carcinoma and renal medullary carcinoma must be diverted early to platinum-based chemotherapy doublets, with a crucial mandate to avoid single-agent ICIs in renal medullary tumors due to risks of hyper-progression. Finally, unclassified tumors with prominent sarcomatoid differentiation remain strong candidates for dual checkpoint blockade. Establishing evidence-based subsequent sequencing algorithms remains a critical unmet need, making ongoing biomarker-matched clinical trials essential.
This short review summarizes recent therapeutic approaches in advanced non-small cell lung cancer lacking actionable genomic alterations presented at the 2026 American Society of Clinical Oncology annual meeting. Particular emphasis was placed on bispecific antibodies and antibody-drug conjugates and their potential to reshape current treatment paradigms. Novel combination treatments have demonstrated promising efficacy with tolerable safety profiles, while small study populations, limited follow-up, and comparator regimens not reflecting current standard of care should be considered when evaluating these findings. Further global trials are needed to determine whether these emerging treatment concepts can overcome current limitations and redefine standards of care.
Major advances in oncology and hematology continue to reshape standards of care, with emerging evidence increasingly challenging established treatment paradigms across a broad spectrum of malignancies. Recent data from the annual meetings of the American Society of Clinical Oncology (ASCO), the European Hematology Association (EHA), and the American Society of Hematology (ASH) have highlighted important developments in targeted therapies, bispecific antibodies, and cellular immunotherapy. This highlight article discusses six studies selected for their potential to influence current and future clinical practice: RASolute 302, investigating targeted therapy in advanced solid tumors; EPCORE FL‑1, evaluating epcoritamab in second-line therapy for follicular lymphoma; the 5‑year follow-up of the phase III CROWN study, assessing lorlatinib in ALK-positive non-small cell lung cancer; EMN30/MajesTEC‑4, exploring frontline therapy for multiple myeloma; and emerging cellular immunotherapies targeting MAGE-A4/MAGE-A8 and the novel RevCAR-T-cell platform. Collectively, these studies illustrate the rapid evolution toward more precise, durable, and personalized cancer treatment.
Summary Major advances in oncology and hematology continue to reshape standards of care, with emerging evidence increasingly challenging established treatment paradigms across a broad spectrum of malignancies. Recent data from the annual meetings of the American Society of Clinical Oncology (ASCO), the European Hematology Association (EHA), and the American Society of Hematology (ASH) have highlighted important developments in targeted therapies, bispecific antibodies, and cellular immunotherapy. This highlight article discusses six studies selected for their potential to influence current and future clinical practice: RASolute 302, investigating targeted therapy in advanced solid tumors; EPCORE FL‑1, evaluating epcoritamab in second-line therapy for follicular lymphoma; the 5‑year follow-up of the phase III CROWN study, assessing lorlatinib in ALK -positive non-small cell lung cancer; EMN30/MajesTEC‑4, exploring frontline therapy for multiple myeloma; and emerging cellular immunotherapies targeting MAGE-A4/MAGE-A8 and the novel RevCAR-T-cell platform. Collectively, these studies illustrate the rapid evolution toward more precise, durable, and personalized cancer treatment.
The treatment algorithm for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC) is rapidly evolving, as shown by the approval of three new agents in 2025: inavolisib, imlunestrant and datopotamab-deruxtecan. Endocrine therapy (ET) is the cornerstone of systemic treatment, while chemotherapy is generally reserved for later lines of treatment, particularly since the combination of ET and CDK4/6 inhibitors has shown remarkable efficacy in the first-line setting, outperforming both single agent and polychemotherapy. Improved understanding of the mechanisms underlying endocrine resistance, including aberrant activation of the PI3K/AKT/mTOR pathway and acquired ESR1 gene mutations, has led to the development and integration of targeted agents into the treatment landscape of HR-positive, HER2-negative MBC. The PIK3CA inhibitor inavolisib, in combination with palbociclib and fulvestrant, has been established as a new treatment standard for patients with endocrine-resistant, PIK3CA-mutated HR-positive, HER2-negative MBC. Likewise, the oral selective estrogen receptor degrader (SERD) imlunestrant has broadened treatment options for patients with ESR1-mutated disease, after progression on ET, regardless of prior CDK4/6 inhibitor exposure. Antibody–drug conjugates (ADCs) have also reshaped the therapeutic landscape, progressively replacing conventional chemotherapy and shifting its use to later lines of treatment. Together with trastuzumab-deruxtecan and sacituzumab-govitecan, datopotamab-deruxtecan has become the third ADC approved for the treatment of patients with HR-positive, HER2-negative MBC. Collectively, these advances reflect a dynamic and rapidly expanding treatment landscape. However, optimal sequencing strategy remains undefined. This short review aims to provide an overview of the three recently approved agents and offers a glimpse into future therapeutic strategies for HR-positive, HER2-negative MBC.
