Citations

Background: Stromal hyaluronic acid (HA) poses a physical barrier and protects tumor cells from immune surveillance. Stroma targeting with pegylated human recombinant PH20 hyaluronidase (PEGPH20) demonstrated improved infiltration of cytotoxic T-lymphocytes and delivery of chemotherapy and PD1/PD-L1 antibodies in tumor models. This multicenter phase II study of PEGPH20 plus pembrolizumab evaluated the efficacy, safety and immune and stromal biomarkers in patients with HA-high refractory metastatic pancreatic ductal adenocarcinoma (mPDA). Patients and Methods: Patients were treated with PEGPH20 3 µg/kg IV weekly and pembrolizumab 200 mg IV in 3-week cycles. Tumor and blood samples were collected at baseline and on-study for biomarker analyses. Results: Between May and November 2019, 38 patients were screened and 8 treated, with median age 68 years (range 60–73) and median two (range 1–4) prior therapies. The study was closed to accrual early by pharmaceutical sponsor. Treatment was well tolerated, with expected grade 1/2 musculoskeletal toxicities. Best response was stable disease in 2 of 7 evaluable patients (29%). Median overall and progression-free survival were 7.2 months (95% CI 1.2–11.8) and 1.5 months (95% CI 0.9–4.4), respectively. Prolonged survival (range 10.2–27.6 months) occurred in patients treated with subsequent chemotherapy. Higher baseline tumor T cell receptor (TCR) clonality correlated with longer survival. Conclusions: Pembrolizumab with PEGPH20 was safe but did not have significant efficacy in refractory HA-high metastatic PDA.

Background The role of dose escalation of radiotherapy (RT) in unresectable stage III NSCLC followed by immunotherapy is unclear. The objective of the current study is to investigate if intermediate dose escalation (IDE) is beneficial in stage III NSCLC patients who receive definitive concurrent chemoradiation (dcCRT) followed by immunotherapy. Materials and methods The study used data from the National Cancer database. Multivariable Cox regression analysis was used to assess the all-cause mortality of patients who received standard RT dose (SD) (60 Gy ± 10%) and IDE (64–74 Gy). Results 47,315 patients were diagnosed in the era before immunotherapy and received dcCRT only, while 4,947 patients were treated with dcCRT and immunotherapy. In the cohort with dcCRT only, patients who received SD had statistically significant worse mortality but clinically minimal difference compared to patients with IDE (HR: 1.09, 95% CI: 1.07-1.12; p<0.0001). In the era of immunotherapy, SD was still associated with worse mortality compared to IDE (HR: 1.17, 95% CI: 1.03-1.33; p=0.02). However, the survival benefit associated with IDE was only restricted to patients who started immunotherapy within six weeks after RT completion (HR: 1.26, 95% CI: 1.05-1.6; p=0.01). There was no difference in mortality between SD and IDE among patients who started immunotherapy between 7–10 weeks (HR: 1.13, 95% CI: 0.88-1.45; p=0.35) or >10 weeks after RT completion (HR: 0.74, 95% CI: 0.51-1.07; p=0.11). Conclusion IDE of RT is not needed for patients diagnosed with stage III unresectable NSCLC who receive immunotherapy > six weeks after dcCRT.

We present a subset analysis on the adolescent cohort of the S1826 randomized phase three trial, comparing nivolumab, doxorubicin, vinblastine, dacarbazine (N-AVD) to brentuximab vedotin-AVD (BV-AVD) in newly diagnosed advanced-stage (AS, stages III and IV) classic Hodgkin lymphoma (cHL). Among 994 patients enrolled, 24% (n = 240) were age 12-17 years. The 3-year progression-free survival (PFS) was significantly higher in the N-AVD group (93% [95% CI, 87 to 96]) compared with the BV-AVD group (82% [95% CI, 73 to 88]; hazard ratio, 0.37 [95% CI, 0.17 to 0.80]). One N-AVD and two BV-AVD patients received protocol-specified residual site radiotherapy (RT). Rates of febrile neutropenia and sepsis were low in both groups. Severe immune-related adverse events were infrequent, although thyroid dysfunction was seen in 7% with N-AVD. Sensory neuropathy (grade ≥2) was more frequent with BV-AVD (14% v 7%) by clinician report. Although premature discontinuation of therapy was reported in 12 N-AVD patients and four BV-AVD patients, no PFS events were noted in the N-AVD group. Patient-reported outcomes indicated less toxicity with N-AVD. N-AVD demonstrated high 3-year PFS in adolescents with AS cHL, with minimal RT use. S1826 exemplifies the benefits of harmonized clinical trial protocols, resulting in timely access to novel agents for adolescents.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer provide recommendations for diagnostic workup, staging, and treatment. These NCCN Guidelines Insights highlight recent updates, with a particular focus on changes to systemic therapies and radiation treatment in the NCCN Guidelines for Small Cell Lung Cancer.

The treatment landscape for multiple myeloma (MM) is evolving rapidly and includes several new options. The management must be tailored to the individual. The NCCN Guidelines for MM provide a framework to base decisions regarding diagnosis, workup, treatment, and follow-up of both newly diagnosed and previously treated relapsed/refractory MM. This manuscript outlines the recommendations from NCCN Guidelines for MM specific to newly diagnosed MM (NDMM).

This guideline has been updated. This ASCO Living Guideline is reviewed on an eight-week cycle. Please see the online dynamic version for the latest updates. ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 (online only) for more . PURPOSE To provide updated guidance regarding the therapy for multiple myeloma. METHODS ASCO and Ontario Health (Cancer Care Ontario) convened a joint Expert Panel and conducted an updated systematic review of the literature. RESULTS The updated review identified a total of 161 relevant randomized trials. UPDATED RECOMMENDATIONS Daratumumab therapy may be offered to patients with high-risk smoldering myeloma. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as initial therapy for transplant eligible patients. They should also be offered at least lenalidomide maintenance, with or without daratumumab, carfilzomib, and/or dexamethasone. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as therapy for suitable transplant-ineligible patients. Patients with relapsed or refractory multiple myeloma should be offered triplet therapy or T-cell redirecting therapies according to a set of recommended principles. Additional information is available at www.asco.org/hematologic-malignancies-guidelines .

Abstract Background Cognitive impairment often goes undetected by clinicians due to time constraints, limited expertise, and lack of standardized tools. Structured cognitive assessments improve detection accuracy compared to unstructured clinical judgment. In 2013, the Alzheimer’s Association published recommendations to help primary care clinicians incorporate cognitive assessments into the Medicare Annual Wellness Visit. Since then, advances in cognitive assessment tools, availability of disease‐modifying therapies, and shifting expectations around early diagnosis have highlighted the need for updated guidance. In response, the Alzheimer’s Association is developing an evidence‐based clinical practice guideline for cognitive testing in primary care, using the GRADE approach, informed by a systematic review of the best available evidence. Method A multidisciplinary panel formulated a clinical question to inform the development of this guideline. A systematic review was conducted (search range: 1999‐2024) to evaluate the diagnostic accuracy of ten cognitive tests (5‐Cog, AD8, GPCOG, IQCODE, Mini‐Cog, MIS, MoCA, QDRS, RUDAS, and SLUMS) for the early detection of cognitive impairment (including MCI and dementia), in adults aged 55+ in ambulatory settings. The panel also narratively summarized data on emerging digital tools. Result Forty‐one studies meeting eligibility criteria were included in the systematic review. Results were analyzed separately by test (including short‐IQCODE and short‐MoCA) and for primary care and for ambulatory clinic settings (e.g., neurology, memory disorder clinics), as well as for English and Spanish language, resulting in 21 separate analyses. Only three analyses, all related to MoCA, allowed for meta‐analysis. The panel will use the evidence to inform conditional recommendations for or against each specific test. Conclusion By evaluating the diagnostic performance of selected tests, this guideline aims to support healthcare professionals in primary care settings in effective triaging of individuals who may benefit from further cognitive evaluation. To enhance real‐world applicability, considerations such as administration time, ease of scoring, and diagnostic accuracy ‐ along with appropriate cut‐offs by race/ethnicity, education, and language ‐ should be prioritized. This guideline will be regularly updated over time to reflect emerging evidence and the needs of diverse populations.

Importance Molecular analyses of biospecimens collected from study participants are essential for identifying biomarkers that can tailor treatments to specific subsets of patients who are most likely to benefit. Sharing of data and biospecimens from clinical trials enables personalized, patient-centric use of cancer therapies and accelerates the development of new treatments. Objective To describe obstacles to sharing data and biospecimens and to propose strategies to enhance access and collaboration. Evidence Review This is a Special Communication authored by 53 academic investigators and patient representatives from the breast cancer community with extensive experience in conducting clinical and translational research. The article also evaluates the impact of biomarker research on specifying responsive subpopulations in the 29 registrational clinical trials that have led to approval of a new drug for treatment of breast cancer between 2017 and 2024. Findings Clinical trial participants are increasingly asked to provide tissue and/or body fluid biospecimens for biomarker research that is typically controlled by the sponsoring pharmaceutical company, but published biomarker studies are rare. Among 29 breast cancer registrational studies reported in the past 8 years, none resulted in biomarker research that restricted a drug’s approved indication. Herein, strategies to maximize the value of clinical data and biospecimens contributed by participants are proposed, thereby supporting the shared goals of the pharmaceutical industry and academia to improve patient care. These strategies include (1) establishing coleadership structures involving academia and patients in clinical trial design and conduct, (2) ensuring that informed consent forms state that data and biospecimens will be shared with academia for future research, (3) requiring the sharing of clinical data as a condition for regulatory approval, and (4) enabling access to biospecimens and translational research data for independent studies on biomarkers that may indicate drug efficacy and toxicity. Conclusions and Relevance Data and biospecimen sharing from registrational trials has been suboptimal. Improving clinical data, biospecimens, and biospecimens’ related data sharing requires concrete actions and a multidimensional stakeholder approach to accelerate the impact of clinical cancer research on the quality of patient care.