Chondrosarcomas are rare cartilaginous neoplasms with limited treatment options. Isocitrate dehydrogenase 1/2 (mIDH1/2) mutations occur in 65% of chondrosarcomas. Here we report safety and efficacy of olutasidenib, an mIDH1 inhibitor, evaluated in patients with locally advanced or metastatic mIDH1 chondrosarcoma (Clinicaltrials.gov identifier: NCT03684811). The primary endpoint was objective response rate by tumor evaluation; secondary endpoints included adverse events, progression-free and overall survival. Patients received olutasidenib 150 mg twice daily. Twenty-three patients were enrolled; 16 were diagnosed with conventional chondrosarcoma (cCS). Median age was 57 (range, 30-71) years. In 21 response-evaluable patients, 11 (52%) had stable disease, 8 (38%) had progressive disease, and 2 (10%) were not evaluable. Median progression-free survival (mPFS) was 2.0 months (95% confidence interval [95%CI]: 1.7, 4.7); median overall survival was 16.0 months (95%CI: 7.7, not reached). Among patients with cCS, 10 (63%) had stable disease; 6 (38%) had progressive disease; mPFS was 3.5 months (95%CI: 1.7, 5.1). Median overall survival in cCS patients was 19.0 months (95% CI: 7.7, not reached). No dose-limiting toxicities were reported during the study. Olutasidenib was well tolerated and conferred disease control in cCS. Study limitations include open-label design and low patient sample due to rarity of cCS.

Although multiple studies have demonstrated the accuracy of 68Ga-PSMA-11 PET/CT, its ability to predict survival outcomes and treatment response remains unclear. This study assessed the prognostic value of 68Ga-PSMA-11 PET/CT in staging unfavorable intermediate- or high-risk prostate cancer (PCa) in patients who are candidates for radical prostatectomy. Methods: This prospective multicenter trial supported by the International Atomic Energy Agency enrolled 775 patients across 11 countries with newly diagnosed, unfavorable intermediate- or high-risk PCa. Patients underwent 68Ga-PSMA-11 PET/CT, after which their disease was categorized as N0M0 (no involvement of local nodes and no metastases), N1M0 (pelvic lymph node involvement), or NxM1 (distant metastases). These findings were then compared with clinical follow-up data. Results: Biochemical recurrence rates were 35.4% (N0M0), 68.2% (N1M0), and 77.2% (NxM1). Two-year event-free survival rates were 56.6%, 43.9%, and 26.0% in patients with N0M0, N1M0, and NxM1 disease, respectively. Two-year overall survival rates were 99.3% in patients with N0M0 disease, 99.2% in those with N1M0 disease, and 86.8% in those with NxM1 disease (P < 0.001). 68Ga-PSMA-11 PET/CT status was the only significant prognostic factor for survival outcomes. Conclusion:68Ga-PSMA-11 PET/CT is a robust and independent prognostic marker in patients with unfavorable intermediate- or high-risk PCa and may help tailor treatments and improve outcomes.

In the Phase III TASUKI-52 trial, nivolumab with carboplatin, paclitaxel (CP), plus bevacizumab significantly prolonged progression-free survival (PFS), and resulted in longer overall survival (OS) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). This final analysis evaluated 4-year treatment outcomes in terms of OS, PFS and duration of response (DOR) by investigator assessment and safety, as well as the background characteristics and treatment courses associated with 4-year survivors. Patients were randomized 1:1 to receive nivolumab (n = 275) or placebo (n = 275) in addition to CP plus bevacizumab. With a minimum follow-up of 53.1 months, nivolumab with CP plus bevacizumab continued to show improvement in OS (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.58-0.88) and PFS (HR: 0.61; 95% CI: 0.50-0.74) compared to placebo with CP plus bevacizumab. The 4-year OS rate was 34.7% in the nivolumab arm versus 22.1% in the placebo arm, and the 4-year PFS rate was 13.7% in the nivolumab arm versus 3.3% in the placebo arm. Among 4-year survivors, the median DOR was numerically longer in the nivolumab arm than in the placebo arm (34.7 vs. 13.5 months). No new safety signals were observed. Four-year survival in the nivolumab arm was associated with the absence of bone metastases and age < 65, but not with PD-L1 status and tumor size. In conclusion, treatment with nivolumab demonstrated long-term survival benefit and durable response, which supports nivolumab with CP plus bevacizumab as a first-line treatment option for advanced nonsquamous NSCLC. Trial Registration: ClinicalTrials.gov identifier: NCT03117049.

Proton therapy offers potentially improved normal tissue sparing compared to photon-based whole-pelvic radiotherapy (WPRT) for high-risk prostate cancer, but its sensitivity to anatomical and setup variations raises concerns about robustness. The aim of this study was - within the setting of a multicentre randomised clinical trial - to explore whether the dose-volume advantages of proton therapy persisted when subject to inter-fractional variation.

The SORASTOP study reports long-term outcomes following planned sorafenib discontinuation in responding patients with extremity desmoid-type fibromatosis (DTF).

Pancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of venous thromboembolism (VTE), which is burdensome and associated with decreased survival. Although neoadjuvant treatment is increasingly used in patients with PDAC, data on VTE in this setting remain scarce. This study evaluated VTE incidence during (neo)adjuvant therapy for resectable and borderline resectable PDAC and its relation to survival.

Intratumoral delivery of NBTXR3 radioenhancer followed by radiation therapy (RT) previously demonstrated safety and feasibility in cisplatin-ineligible and cetuximab-ineligible patients with locally advanced head and neck squamous cell carcinoma (HNSCC) in a dose-escalation phase 1 study.

Programmed cell death 1 protein (PD-1) or programmed cell death 1 ligand 1 inhibitors plus chemotherapy is the current standard first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). However, the long-term survival benefits at the 5-year benchmark remain uncertain.

Combined inhibition of AKT and the androgen receptor (AR) might be more efficacious than AR inhibition alone in biochemical recurrence (BCR) of prostate cancer (PC) by additive effects on the two effector pathways.

Advanced biliary tract cancer (BTC) is an aggressive malignancy, and often presents with poor prognostic outcomes despite standard chemotherapy. This study aimed to evaluate the preliminary efficacy and safety of toripalimab in combination with gemcitabine + oxaliplatin (GEMOX) as a first-line treatment option for advanced BTC.

Neoadjuvant ipilimumab plus nivolumab has become standard therapy for stage III melanoma based on the NADINA trial, although long-term data are lacking. In the phase 2 PRADO cohort of OpACIN-neo, 99 patients with stage III macroscopic melanoma received this regimen. Here we report first-time 5-year survival data: 71% event-free survival, 74% relapse-free survival, 79% distant metastasis-free survival and 86% overall survival. Ongoing grade 1-2 immune-related adverse events occurred in 69% of patients alive, predominantly vitiligo and hypothyroidism. Major pathologic response (MPR), high tumor mutational burden (TMB), high interferon-gamma (IFNγ) signature and programmed cell death ligand 1 (PD-L1) expression of 1% or higher were associated with favorable outcomes. Combined high TMB, IFNγ and PD-L1 expression yielded 100% MPR and 100% 5-year event-free survival, whereas triple low expression had only 18% MPR and 41% event-free survival. Our findings demonstrate favorable long-term outcomes for patients with an MPR and identify IFNγ and PD-L1 as promising baseline biomarkers. ClinicalTrials.gov identifier: NCT02977052 .

Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is characterised by hyperactivation of the cyclin-dependent kinase 4/6 (CDK4/6) pathway. As immunotherapy has become the first-line treatment for HNSCC, resistance to anti-programmed death-1 (PD-1) agents has emerged as a pivotal challenge. This prospective, single arm, phase II study (NCT05721443) evaluated the efficacy and safety of dalpiciclib, a CDK4/6 inhibitor, combined with cetuximab in patients with anti-PD-1-resistant, HPV-negative recurrent and/or metastatic HNSCC. Patients diagnosed with p16-negative R/M HNSCC resistant to first-line anti-PD-1 therapy without prior cetuximab treatment were enroled. Patients received oral dalpiciclib (150 mg daily on days 1-21 of each 28-day cycle) and intravenous cetuximab (400 mg/m2 on day 1 of cycle 1, followed by 250 mg/m2 weekly in each cycle). The primary endpoint was objective response rate (ORR), secondary endpoints were overall survival, progression-free survival, duration of response, and safety. Between March 2023 and November 2024, a total of 28 patients were enroled. The ORR was 67.9% (19/28; 95% confidence interval [CI], 49.0%-82.0%), which met our primary endpoint. With a median follow-up of 9.2 months (interquartile range [IQR], 5.98-14.12), the median progression-free survival was 7.0 months (95% CI, 4.13- not reached [NR]), and the median overall survival was 17.0 months (95% CI, 10.75-23.25). Treatment-related adverse events (TRAEs) occurred in all patients, predominantly grade 1-2. Grade 3 TRAEs included neutrophil count decreased (9/28, 32.1%) and white blood cell count decreased (9/28, 32.1%). No grade 4 or 5 TRAEs were observed. Dalpiciclib combined with cetuximab was well-tolerated and showed promising efficacy in patients with anti-PD-1-resistant, HPV-negative recurrent and/or metastatic HNSCC.

The first-line (1L) standard of care for B-Raf proto-oncogene (BRAF)V600E-mutant metastatic non-small cell lung cancer is BRAF inhibitor dabrafenib with MEK inhibitor trametinib (D + T). Combination therapy with encorafenib and binimetinib (E + B) has recently demonstrated clinical benefit in this setting in the single-arm, phase II PHAROS trial. We evaluated the relative efficacy and safety of E + B versus D + T in 1L using an unanchored matching-adjusted indirect comparison.

ABM-1310 is an investigational, orally bioavailable BRAF V600 inhibitor with high blood-brain barrier (BBB) penetration.

Dual anti-human epidermal growth factor receptor 2 (HER2) therapy plus chemotherapy followed by maintenance treatment with HER2-targeted and endocrine therapies is standard first-line treatment for hormone-receptor-positive, HER2-positive metastatic breast cancer. On the basis of preclinical and clinical data, the addition of palbociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) may overcome resistance to both endocrine and HER2-directed therapies.

Translational Breast Cancer Research Consortium 048 was a proof-of-principle trial demonstrating responses to the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in patients (pts) with metastatic breast cancer (MBC) with germline (g) PALB2 or somatic (s) BRCA mutations (sBRCAm). Here we report results from the expansion cohorts in a larger sample of pts with gPALB2m or sBRCAm.

Neoadjuvant immunotherapy combined with chemotherapy is an emerging strategy for improving outcomes in patients with locally advanced gastric cancer (LAGC). However, clinical evidence regarding the efficacy of serplulimab plus SOX chemotherapy and its immunologic correlates remains limited.

The efficacy and safety of anti-HER2 therapy and immune checkpoint inhibitors combined with chemotherapy to treat HER2-positive advanced breast cancer that has failed standard HER2-directed therapies is unknown. This study evaluated the efficacy and safety of a novel, fully China-developed combination therapy-comprising inetetamab (an anti-HER2 monoclonal antibody), camrelizumab (an anti-PD-1 antibody), and utidelone (a microtubule inhibitor)-in this treatment-refractory population.

CDK4/6 inhibitors (CDK4/6i) improve outcomes for estrogen receptor (ER) positive/HER2-negative breast cancers (BCs), yet intrinsic and acquired resistance exist. Here, we evaluated anastrozole in combination with palbociclib (ANA/PAL) in the NeoPalAna Endocrine-Resistant cohort (NCT01723774). Thirty-four patients with clinical stage II/III ER + /HER2- BCs resistant to standard neoadjuvant endocrine therapy (on-treatment Ki67 > 10%) received neoadjuvant ANA/PAL, with serial biopsies analyzed. The primary endpoint, complete cell cycle arrest (CCCA; Ki67C1D15 ≤ 2.7% at cycle 1, day 15), was achieved in 57.6% of patients (95%CI: 39.2-74.5%). Resistance to ANA/PAL (Ki67C1D15 > 10%) was associated with higher pre-treatment tumor grade, Ki67, and specific PAM50 subtypes. Resistant tumors demonstrated reduced ER signaling and upregulation of cell cycle, mTOR, interferon, JAK/STAT, and immune checkpoints. Additionally, a 33-gene signature that predicted neoadjuvant Ki67 response to ANA/PAL was prognostic in a metastatic validation cohort. These findings underscore dysregulated oncogenic pathways as potential resistance mechanisms and biomarkers of response to CDK4/6i.

Non-metastatic lymphadenopathy is challenging to diagnose. The comparative diagnostic performance of endobronchial ultrasound (EBUS)-guided transbronchial mediastinal cryobiopsy (TBMC) vs. EBUS-transbronchial needle aspiration (TBNA) remains debated.