To evaluate the morbidity of sentinel lymph node (SLN) biopsy with carbon nanoparticle suspension mapping compared to pelvic lymphadenectomy in patients with early-stage cervical cancer.

Cyclin-dependent kinase 4/6 inhibitors with endocrine therapy are standard first-line therapy for patients with hormone receptor-positive metastatic breast cancer. Older patients, especially the frailer subpopulation, are underrepresented in clinical trials, limiting data on treatment and safety outcomes in this population.

The ABC-07 phase II randomised controlled trial (ISRCTN: 10639376) investigated the addition of stereotactic body radiotherapy (SBRT) to systemic chemotherapy in locally advanced biliary tract cancers (BTCs). We report the radiotherapy quality assurance (RTQA) of SBRT treatment plans in the trial.

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.

Patients with tumor mutational burden (TMB)-high tumors can derive benefit from atezolizumab, though previous studies have used inconsistent TMB cutoffs. We report data for atezolizumab in patients with TMB-high solid tumors from the phase II TAPISTRY multicohort trial, using TMB cutoffs of ≥13 and ≥16 mutations per megabase (mut/Mb).

Low vitamin D status and inflammation are associated with poor prognosis among colorectal cancer (CRC) patients. We assessed the efficacy of personalized vitamin D3 supplementation (VIDS) for reducing inflammation in patients with low vitamin D status.

Individuals with non-small-cell lung cancer (NSCLC) with metastases to the ipsilateral mediastinum or subcarinal lymph nodes (N2 disease) have poor long-term survival. This exploratory analysis from the randomized phase 3 CheckMate 77T study assessed clinical outcomes by nodal status in individuals with stage III NSCLC who received neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab (nivolumab) versus neoadjuvant chemotherapy followed by surgery and adjuvant placebo (placebo). Here we show that among patients with N2 disease, nivolumab versus placebo improved event-free survival (1-year rate, 70% versus 45%; hazard ratio, 0.46 (95% confidence interval, 0.30-0.70)) and pathological complete response rate (22.0% versus 5.6%); 77% versus 73% had definitive surgery, of whom 84% versus 74% received a simple lobectomy. Furthermore, nivolumab improved outcomes versus placebo in patients with multistation N2 NSCLC (1-year event-free survival rate: 71% versus 46%; hazard ratio, 0.43 (0.21-0.88); pathological complete response rate, 29.0% versus 2.7%). In the N2 subgroup with definitive surgery, 67% and 59% of patients had nodal downstaging after surgery (57% versus 44% downstaged to node-negative disease). Median EFS in randomized patients with stage III non-N2 NSCLC was not reached with nivolumab and 17.0 months with placebo (1-year EFS rate, 74% versus 62%; hazard ratio, 0.60 (0.33-1.08)). No new safety signals were identified. These findings support perioperative nivolumab plus neoadjuvant chemotherapy as an efficacious treatment for stage III N2 disease and suggest that N2 status may not predict poor prognosis in resectable NSCLC treated with perioperative immunotherapy. ClinicalTrials.gov identifier: NCT04025879 .

The primary aim of this study was to investigate the malignancy detection rate of [68Ga]Ga-SSO120 ([68Ga]Ga-satoreotide trizoxetan) PET/CT in patients with small cell lung cancer (SCLC) and large cell neuroendocrine lung cancer (LCNEC). Secondary aims included investigations of lesion-based detection rates and quantification. Methods: In this prospective, phase 2, cross-sectional imaging trial, 21 [68Ga]Ga-SSO120 PET/CTs were performed for 19 patients. Overall detection rates, lesion-based detection rates, and number of identified lesions were compared between [68Ga]Ga-SSO120 PET and CT. The [68Ga]Ga-SSO120 SUVmax, SUVpeak, SUVmean, and tumor-to-liver ratios in malignant lesions and selected normal tissue were quantified. Results: Nineteen patients (16 with SCLC, 2 with LCNEC, and 1 with combined SCLC/LCNEC) were scanned during palliation chemotherapy (n = 11) or surveillance (n = 8). [68Ga]Ga-SSO120-detectable lesions were identified in 18 patients (95%). Sensitivity in the lungs, regional lymph nodes, and extrathoracic regions was 82%, 83%, and 93%, respectively. [68Ga]Ga-SSO120 PET detected significantly fewer lesions than did CT (P = 0.037), particularly small lung lesions, regional lymph nodes, and liver lesions. In contrast, [68Ga]Ga-SSO120 PET identified 10 additional metastases in 5 patients (bone, 7; cerebellum, 1; subcutaneous, 2). SUVmax (median, 7.4; range, 4.6-26.4) was not significantly associated with time since diagnosis, time since last chemotherapy, number of treatment cycles, or current progression. Conclusion: [68Ga]Ga-SSO120 PET/CT successfully visualized SCLC and LCNEC lesions during and after chemotherapy. Therapeutic studies with [177Lu]Lu-SSO110 ([177Lu]Lu-satoreotide tetraxetan), the theranostic companion of [68Ga]Ga-SSO120, PET are warranted.

Stereotactic body radiotherapy (SBRT) is effective for localised prostate cancer but increases genitourinary adverse events (AE). Focal boost to the dominant lesion may improve disease control. The DESTINATION study investigates whole gland dose de-escalation, with focal boost, using MR-guided adaptive radiotherapy (MRgART), to maintain cancer control whilst demonstrating acceptable AE.

The ability of IL12 to stimulate production of IFNγ suggested it might improve the efficacy of low-dose IFNα. In this phase II trial, patients with metastatic malignant melanoma were administered recombinant human (rh) IL12 followed by IFNα2b. Primary endpoints were clinical response and progression-free survival. Secondary objectives were to evaluate the effect of endogenous IFNγ on JAK-STAT signaling and IFN-regulated genes in peripheral blood mononuclear cells (PBMC). Patients with advanced melanoma received rhIL12 on day 1 and IFNα2b on days 2 to 6 of a 14-day cycle. rhIL12 was given intravenously at 300 ng/kg. IFNα2b was dosed at 3 × 106 units subcutaneously. Plasma IFNγ was assayed by ELISA; JAK-STAT signaling was measured in PBMCs by flow cytometry. The proportion of responders was assessed via Simon two-stage design. Thirty-eight patients were enrolled. The regimen was well-tolerated. Two patients achieved a partial response lasting 6 months or longer (5.3%). IL12 administration led to an increase in mean plasma IFNγ from 33.57 pg/mL at baseline to a maximum of 564.86 pg/mL and increased expression of STAT1 and STAT2 in PBMCs. Generation of phosphorylated STAT1 and IFN-simulated gene product 15 in response to IFNα was enhanced following IL12. rhIL12 given prior to IFNα2b stimulated production of IFNγ, which led to increased levels of JAK-STAT signaling intermediates in patient PBMCs. Combination therapy was reasonably well-tolerated but conferred marginal benefit in patients with metastatic melanoma. These results can inform future studies that use recombinant IL12 or novel IL12 constructs.

We report 5-year results of the phase III randomized TRIPLETE study. Eligible patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) received first-line modified fluorouracil, leucovorin, oxaliplatin (mFOLFOX)/panitumumab (control group, n = 217) versus modified fluorouracil, leucovorin, oxaliplatin, irinotecan (mFOLFOXIRI)/panitumumab (experimental group, n = 218). We present overall survival (OS) and updated outcomes in the intention-to-treat population. The median follow-up was 60.2 months (IQR, 49.3-70.0). The median OS was 41.1 and 33.3 months for experimental and control groups, respectively (hazard ratio [HR], 0.79 [95% CI, 0.63 to 0.99]; P = .049). OS outcomes favored the experimental group regardless of clinical features. No differences in objective response rate (primary end point; 75%/78%, odds ratio, 0.84 [95% CI, 0.54 to 1.31]; P = .442), early tumor shrinkage rate (P = .954), depth of response (P = .573), no residual tumor resection rate (P = .329), and progression-free survival (HR, 0.95 [95% CI, 0.78 to 1.16]; P = .606) were confirmed. Among patients alive at the time of disease progression, the median postprogression survival was 24.6 and 17.7 months for experimental and control groups, respectively (HR, 0.79 [95% CI, 0.62 to 1.01]; P = .062). Similar proportions of patients in both groups received subsequent lines of therapy (control/experimental: second line 73%/71%, third line 51%/49%, fourth line 31%/32%), as well as nonpalliative locoregional treatments (control/experimental: 16%/16%). Upfront mFOLFOXIRI/panitumumab significantly improves OS compared with mFOLFOX/panitumumab in patients with RAS/BRAF wild-type mCRC.

Combined mTOR and MEK inhibition, critical components of the RAS effector pathway underlying the pathogenesis of neurofibromatosis type 1 (NF1)-related tumors, caused regression in a malignant peripheral nerve sheath tumor (MPNST) transgenic mouse model. The primary objective was to determine the clinical benefit rate in patients with unresectable/metastatic MPNST.

Aromatase inhibitors (AI) are used to treat estrogen receptor (ER)-positive low-grade endometrioid endometrial cancer. In breast cancer, ESR1 mutations are rare at diagnosis (<5%) but are frequently acquired in AI-resistant cases and are considered one of the major resistance mechanisms to endocrine therapy. This study aimed to assess the prevalence of ESR1 mutations in hormonotherapy-naïve endometrial cancer samples and correlate them with molecular profiles, ER expression, and clinical outcomes.

Establish the safety, tolerability, and preliminary activity of trastuzumab deruxtecan (T-DXd) in combination with other anticancer therapies in human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (mBC).

B-cell maturation antigen (BCMA)-targeting therapies provide a new approach to treating multiple myeloma (MM). Alnuctamab (ALNUC) is a 2 + 1 immunoglobulin G1-based bispecific antibody binding BCMA and CD3ε receptors on myeloma and T cells, respectively. CC-93269-MM-001 is a first-in-human, phase 1 dose escalation/expansion study investigating ALNUC in relapsed/refractory MM. Patients had ≥3 prior regimens, disease progression ≤60 days of last regimen, and were BCMA-directed therapy-naïve. ALNUC was administered intravenously (IV) and subcutaneously (SC); however, SC was selected for further evaluation due to the more favorable safety profile. Ninety-five patients received ALNUC SC; at data cutoff, 44.2% remained on treatment and median follow-up was 8.0 months. The recommended phase 2 dose was 30 mg. The most common treatment emergent adverse events (any grade/grade 3/4) were CRS (57.9%/0%), and neutropenia (53.7%/43.2%). Infections were also frequent (64.2%/14.7%). ORR was 58.9% for all ALNUC SC-treated patients and 71.4% for the 30-mg cohort; 47/95 (49.5%) were measurable residual disease (MRD) negative. Overall, the safety and efficacy of ALNUC SC were comparable to other BCMA-targeted therapies. These results support improved safety of SC versus IV, and corroborate a step-up dosing strategy to mitigate CRS. Importantly, a schedule that de-intensifies over time provides favorable toxicity that may be applicable to other bispecific engagers.

Postoperative recurrence significantly impacts long-term survival in patients with resectable hepatocellular carcinoma (HCC). In this single-arm, phase II trial (NCT04834986), 27 patients with resectable HCC at high recurrence risk received perioperative tislelizumab (anti-PD-1) plus lenvatinib (multi-kinase inhibitor). Co-primary endpoints were safety and feasibility. Secondary endpoints included objective response rate (ORR), 1-year and 2-year disease-free survival (DFS), median DFS, and pathologic complete response (pCR). Post-hoc exploratory machine learning analyses identified potential predictive factors. The regimen was feasible and generally well tolerated; grade 3 treatment-related adverse events occurred in 7.4%. ORR was 55.6%. Among 20 patients undergoing surgery, The Median DFS was 18.8 months (20.1-month follow-up), with 1- and 2-year DFS of 74.0% and 49.8%, and 20% achieved pCR. No unexpected safety signals were observed. The post-hoc machine learning model based on Tabular Prior Data Fitted Network, comprising six pretreatment hematological measures, demonstrated classification of candidate selection in the training set (area under the curve [AUC], accuracy [ACC], and average precision [AP], all 1.0) and the test set (AUC = 0.917, ACC = 0.778, AP = 0.966). In conclusion, tislelizumab-lenvatinib is a potential perioperative regimen for resectable HCC at high recurrence risk, showing preliminary efficacy and safety.

This single-arm, phase I/II trial aimed to evaluate the efficacy and safety of firmonertinib plus anlotinib as first-line treatment for patients with non small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations.

In NSCLC, TP53 mutations are heterogeneous with varied effects on protein synthesis, function and clinical outcomes. We hypothesize that a refined classification of TP53 mutations, beyond binary categorization, could improve prognostication. Furthermore, specific mutations could be associated with enhanced benefit from immune checkpoint inhibitors (ICI) versus chemotherapy. To investigate this, we analyzed data from randomized trials (OAK and POPLAR) which compared atezolizumab to chemotherapy in previously treated advanced driver-negative NSCLC.

Neoadjuvant camrelizumab plus apatinib has shown a promising major pathological response (primary endpoint) and pathological complete response (a secondary endpoint) in patients with resectable stage IIA-IIIB non-small-cell lung cancer (NSCLC) in a previous single-arm phase 2 trial. Here, we present the 3-year survival outcomes and potential prognostic factors with extended follow-up.

In the previously completed NCI9673 (part A) single-arm study, the antiprogrammed death (PD)-ligand-1 antibody nivolumab demonstrated efficacy for patients with metastatic anal cancer. In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer.