Elranatamab, approved for relapsed or refractory multiple myeloma, demonstrated deep, durable responses and manageable safety in patients without prior B-cell maturation antigen (BCMA)-directed therapy (BCMA-naive) in MagnetisMM-3 (NCT04649359). This post hoc analysis evaluated efficacy and safety in the US subgroup. Following step-up dosing, patients received 28-day cycles of elranatamab 76 mg once weekly. After ≥6 cycles, patients with partial response or better persisting for ≥2 months transitioned to every 2 weeks, then to every 4 weeks after ≥6 every-2-week cycles. This analysis included all US-enrolled BCMA-naive patients who received ≥1 elranatamab dose. Of the 123 evaluable patients, 47 were enrolled in the United States (38.2%). At a median follow-up of 39.6 months, the objective response rate was 66.0% (95% CI, 50.7-79.1); 42.6% (95% CI, 28.3-57.8) achieved complete response or better. Median (95% CI) duration of response, progression-free survival, and overall survival were 40.8 (24.0-not estimable [NE]), 27.3 (4.3-NE), and 43.6 (14.9-NE) months, respectively. Common (≥60%) treatment-emergent adverse events (any grade; grade 3/4) included infections (70.2%; 42.6%), fatigue (61.7%; 8.5%), and cytokine release syndrome (61.7%; 0%). Twenty-two patients switched from once weekly to every-2-week dosing, then eight switched from every-2-week to every-4-week dosing. Of 18 responders who switched from once weekly to every-2-week dosing and eight responders who further reduced to every 4 weeks, 77.8% and 87.5%, respectively, maintained or improved their response for ≥6 months thereafter. Elranatamab demonstrated durable responses and manageable safety in the heavily pretreated US subgroup, consistent with the overall MagnetisMM-3 BCMA-naive population.

A recent meta-analysis reported that patients with ovarian cancer have a 3-fold increase in the risk of diagnosis of depression compared to the general population. However, the role of disease-related processes in depressive symptoms-particularly at diagnosis versus after treatment-remains unclear. This study aimed to examine the contribution of somatic symptoms to the assessment of depression severity in patients with ovarian cancer, both at diagnosis and 1 year later, compared to healthy controls. A total of 428 patients with ovarian cancer completed psychosocial assessments at 1-2 weeks before surgical intervention or initiation of neoadjuvant chemotherapy and at a 1-year follow-up visit. A comparison sample from the Midlife in the United States study was included. Item factor analysis was used to examine the functioning of somatic items in a common depression symptom index in both samples. Somatic items demonstrated differential functioning between groups. Specifically, patients with ovarian cancer were more likely to endorse somatic symptoms at lower levels of depression as compared to healthy aging adults; they additionally required a lower level of depression to endorse somatic items as compared to nonsomatic items. These differences between patients with cancer and healthy aging adults were no longer present at 1 year postdiagnosis. These findings support the conclusion that somatic symptoms may disproportionately inflate depression scores among patients with ovarian cancer at diagnosis, which may potentially lead to misclassification or overestimation of depression severity. This highlights the need for refined measurement approaches that account for the somatic burden of cancer in assessing depression during active disease.

This study evaluates baseline inflammatory biomarkers prognostic of clinical outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Lutetium-177 (177Lu)-PSMA-617. A retrospective review of patients treated with 177Lu-PSMA-617 at Emory Winship Cancer Institute was conducted. Baseline inflammatory markers obtained included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and hemoglobin-to-platelet ratio (HPR). Cox proportional hazards models assessed overall survival (OS) and progression-free survival (PFS), and a logistic regression model assessed ≥50% decline in prostate-specific antigen (PSA) from baseline (PSA50). A prognostic biomarker composite score was generated using best-subset variable selection from a multivariate Cox model. In this cohort of 163 patients (median age 73; 51.6% White, 43.6% Black) with mCRPC treated with 177Lu-PSMA-617, elevated NLR, PLR, PIV, SII, and reduced HPR were independent prognostic biomarkers of shortened OS (NLR hazard ratio [HR], 2.7, p=.002; PLR HR,2.08, p=.015, PIV HR,2.86, p=.002, SII HR,2.5, p=.003; and HPR HR,0.43, p=.011). Higher NLR, PLR, and SII values were independently prognostic of shortened PFS (NLR HR,1.82, p=.012; PLR,1.6, p=.036; and SII HR,1.85, p=.009). Patients with elevated HPR and hemoglobin (Hgb) had higher odds of PSA50 response (HPR: 84.8% vs. 15.2%, p=.032, median Hgb of PSA50 response: 11.5 vs. 10.7, p=.01). The biomarker composite score stratified overall survival with good discrimination (C-index=0.732), demonstrating a reduction in mortality risk from the high-tercile group to intermediate-tercile (HR, 0.40, p=.022) and low-tercile (HR,0.16, p<.001). Baseline inflammatory markers are associated with clinical outcomes for patients treated with 177Lu-PSMA-617.

It has been suggested that baseline tumor burden may correlate with immune checkpoint inhibitor (ICI) outcome for individual tumor types in which ICIs are standardly used. The authors investigated whether pretreatment tumor burden correlates with overall survival (OS), progression-free survival (PFS), and tumor regression among patients who had rare cancers treated with dual ICIs. Southwest Oncology Group study S1609 was a phase 2, National Cancer Institute/Southwest Oncology Group basket study (>1000 sites) evaluating nivolumab plus ipilimumab in 53 cohorts of patients who had rare/ultrarare malignancies (ClinicalTrials.gov identifier NCT02834013). Overall, 722 patients were included in this secondary analysis, all of whom had measurable disease (Response Evaluation Criteria in Solid Tumors, version 1.1). Baseline tumor burden, defined as the sum of the greatest dimensions of target lesions at study registration, was analyzed based on quartiles observed in the data. The number of target lesions was also considered a secondary tumor burden measure. End points included OS and PFS. Larger baseline tumor burden correlated with shorter OS, but not PFS (multivariable analysis). Higher baseline tumor burden quartiles had only a weak negative association with any tumor regression at first scan (Fisher exact test, p=.09), and multivariable analyses further indicated that both tumor burden and any tumor regression at first posttreatment scan were independently associated with OS in multivariable analysis (comparing a baseline tumor size ≥12.9 cm vs. 1.0-4.8 cm; hazard ratio, 1.64; 95% confidence interval, 1.02-1.72; p=.032), but there was no evidence of an interaction between tumor burden and any tumor regression at the first scan (p for interaction>.65). Larger baseline tumor burden was associated with worse OS, but not PFS, and was not predictive of tumor regression after dual ICI therapy in a large cohort with rare cancer types.

This news section offers Cancer readers timely information on events, public policy analysis, and topical issues. In this issue, according to results of the phase 3 MajesTEC‐3 trial, the combination of teclistamab plus daratumumab in patients with early relapsed myeloma significantly improved progression‐free survival and led to an overall survival advantage in comparison with the standard of care in patients with relapsed or refractory multiple myeloma. In addition, ASTRO recently published its first clinical guideline focused on the use of radiation therapy in patients with gastric cancer, and a reduced induction dose of daunorubicin is a potential standard for pediatric patients with ALL.

In the delivery of cancer care, patients may experience modifications to their intended chemotherapy regimen for reasons such as toxicity, tolerability, and scheduling challenges. Understanding modifications from the intended chemotherapy in the real-world setting of cancer care may affect treatment planning and inferences of real-world treatment effectiveness. By leveraging data from the Optimal Breast Cancer Chemotherapy Dosing Study, this research studied 12,558 women receiving chemotherapy for primary stage I-IIIA breast cancer at Kaiser Permanente Northern California (2006-2019) and Kaiser Permanente Washington (2004-2015). Modifications in chemotherapy administered from intended, both overall and by regimen, are described. Prevalence ratios (PRs) were calculated for associations between regimen attributes and treatment modifications via generalized linear models of the Poisson family with a log-link function and robust standard errors. Intent to receive a guideline-concordant regimen was associated with a lower likelihood of modifications from the intended chemotherapy (vs. non-guideline concordant) (PR, 0.74; 95% CI, 0.69-0.79), as was receiving a dose-dense regimen (vs. non-dose dense) (PR, 0.84; 95% CI, 0.78-0.91). Those receiving any neoadjuvant chemotherapy (vs. adjuvant only) were more likely to have modifications from the intended chemotherapy (PR, 1.29; 95% CI, 1.19-1.41). Increasing numbers of cycles and drugs administered were associated with a higher likelihood of modifications (ptrend < .001). Breast cancer chemotherapy regimens used in the real-world setting were examined. Chemotherapy modifications varied markedly by regimen and by characteristics of the regimen administered. Given that more than one in three women in this cohort did not receive chemotherapy as intended, these novel findings may be informative in treatment planning and for future research assessing real-world treatment effectiveness.

Smoking may negatively affect health-related quality of life (HRQOL) in prostate cancer survivors, even though it is not a smoking-related malignancy. The longitudinal association of smoking with HRQOL was evaluated by focusing on intensity and duration. Patients from the population-based North Carolina Prostate Cancer Comparative Effectiveness and Survivorship Study, enrolled via the state cancer registry (2011-2013), were analyzed. HRQOL was measured with the Short Form 12 instrument at intervals of up to 5 years posttreatment. Smoking status was self-reported. Linear and mixed-effects models assessed associations with controlling for age, treatment, and time. Of 842 participants, 474 underwent prostatectomy, 258 had radiation therapy, and 110 had brachytherapy. Concurrent smoking was associated with worse general health, mental health, and physical functioning (all p<.05). Graded analysis revealed a significant dose response, with smoking ≥1 pack/day linked to the greatest declines in general health (β=-3.25; p<.001) and physical functioning (β=-2.35; p=.003) at 5 years. Smoking demonstrates significant concurrent and longitudinal associations with poorer HRQOL in prostate cancer survivors, with a clear dose-response pattern. These results underscore the critical need to integrate structured smoking assessment and cessation support as a core component of comprehensive prostate cancer survivorship care.

Oral cavity cancers are generally considered etiologically similar, with a majority (>75%) attributable to smoking/alcohol. Yet, incidence trends for oral cavity cancers have recently diverged in the United States and several European countries (with declines for most oral cavity cancers but increases for oral tongue cancers), suggesting etiologic differences. This study quantified etiologic heterogeneity across oral cavity cancers using data from the NIH-AARP Diet and Health Study. Cox regression models were used to quantify associations (hazard ratios [HRs] and population attributable fractions [PAFs]) and etiologic heterogeneity for risk factors across oral cavity anatomic sites. Among 490,969 individuals (6,732,760 person-years), 765 incident oral cavity cancers occurred. There was substantial heterogeneity in the associations of smoking and alcohol within constituent oral cavity cancers (HRs for current smokers, >2 drinks/day vs. never-smokers/nondrinkers: floor of mouth=14.7; hard palate and other mouth=8.1; oral tongue=4.9; gum=2.6; lip=1.5). PAFs for smoking/alcohol varied widely, ranging from 12.0% for the lip to 56% for the floor of mouth. We observed unexpected associations of increased oral tongue cancer risk with increased consumption of vegetables: total vegetables without legumes (HR per cup equivalent/day, 1.13; 95% CI, 1.01-1.27); Solanaceae (HR, 1.43; 95% CI, 1.20-1.70); Umbelliferae (HR, 2.31; 95% CI, 1.30-4.12); and dark green leafy vegetables (HR, 1.38; 95% CI, 1.07-1.78). Associations for total vegetables (HR,1.12), Solanaceae (HR,1.26), and dark green leafy vegetables (HR,1.32) were remarkably similar in the PLCO trial, a prospective US cohort of ∼155,000 individuals. The results highlight the need for disaggregation of oral cavity cancer sites in etiologic studies and reappraisal of widely accepted smoking/alcohol relative risks/attributable fractions.

In a large cohort of survivors of childhood cancer, lower risk of premature aging was associated with adherence to health dietary patterns. Future studies of interventions targeting modifiable risk factors (e.g., lifestyle modifications) are needed to improve health outcomes in this important, growing population.

CANCERT he TROP2-targeting antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) significantly improved progression-free survival (PFS) and overall survival (OS) in comparison with pemetrexed plus platinum-based therapy in patients with EGFR-mutated non-small cell lung cancer (NSCLC) that had progressed after an EGFR tyrosine kinase inhibitor (TKI) according to the results of the OptiTROP-Lung04 trial. 1 These findings, which were presented at the 2025 European Society for Medical Oncology Congress by Li Zhang, MD, an oncologist at the Guangdong Provincial Clinical Research Center for Cancer in Guangzhou, China, and were published simultaneously in The New England Journal of Medicine, confirmed the findings from an earlier phase 2 trial of sac-TMT, which showed significant improvements in PFS and OS in comparison with docetaxel. 2 The phase 3 trial enrolled 376 patients with EGFR-mutated locally advanced or metastatic nonsquamous NSCLC that had progressed after a prior EGFR TKI (94.7% of the patients had received a third-generation EGFR TKI).Patients were randomly assigned to sac-TMT or pemetrexed plus platinum-based chemotherapy.The trial enrolled only Asian patients.The final PFS analysis showed a 4-month improvement in median PFS with sac-TMT in comparison with chemotherapy (8.3 vs. 4.3 months; hazard ratio [HR], 0.49; 95% CI, 0.39-0.62).A preplanned interim OS analysis that was conducted at a median follow-up of 18.9 months showed a 40% reduction in the risk for death with sac-TMT versus chemotherapy (HR, 0.60; 95% CI, 0.44-0.82;two-sided p = .001).The median OS was not reached for patients on sac-TMT but was 17.4 months for patients on chemotherapy.The OS rate at 18 months was 65.8% for patients on sac-TMT and 48.0% for patients on chemotherapy.The majority of the patients who discontinued the trial went on to have subsequent anticancer treatment.Approximately half of the patients in the sac-TMT arm (41.9%) and the chemotherapy arm (53.6%) had subsequent chemotherapy.Subsequent ADCs were given to 1.4% of the patients assigned to sac-TMT and to 19.6% of the patients assigned to chemotherapy.The rates of grade 3 or higher treatment-related adverse events were similar for sac-TMT (58.0%) and chemotherapy