In this phase 3 trial, penpulimab combined with chemotherapy was assessed against a regimen of placebo plus chemotherapy for the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). 291 patients were randomised and allocated in a 1:1 ratio in order to receive penpulimab (n = 144; 200 mg) or placebo (n = 147; 200 mg), plus chemotherapy (cisplatin/carboplatin and gemcitabine) every 3 weeks. Patients followed by maintenance therapy with penpulimab or placebo after 6 cycles. The primary endpoint of this study was progression-free survival (PFS) according to RECIST v1.1, and a significantly longer median PFS in the penpulimab arm versus the placebo arm (9.63 versus 7.00 months; hazard ratio 0.45, 95% CI: 0.33-0.62, P < 0.0001) was demonstrated in this prespecified interim analysis. The key secondary endpoint was the overall survival (OS). However, the OS data were still immature, and the median OS was not achieved (hazard ratio, 0.94; 95% CI: 0.63-1.40). The occurrence of treatment-related adverse events (grade ≥ 3) was 89.0% and 85.9% in two arms, with the most common being reduced the quantity of neutrophil (56.2% vs. 62.0%), reduced the quantity of white blood cell (54.1% vs. 54.9%), and anemia (45.2% vs. 38.7%). In the penpulimab arm, 6 patients (4.1%) experienced immune-related adverse events (grade ≥ 3). Adding penpulimab to chemotherapy led to a notable enhancement in PFS for the first-line R/M NPC treatment, alongside a safety profile that was both manageable and tolerable. ClinicalTrials.gov identifier NCT04974398.

Immunotherapy resistance represents a major unmet clinical need for patients with metastatic non-small cell lung cancer (NSCLC). Preclinical studies have identified PCSK9 as an immunosuppressive regulator of antigen presentation, providing a compelling rationale for therapeutic PCSK9 inhibition as a strategy to overcome resistance to immune checkpoint blockade. Building on this evidence, we present the scientific rationale and study design of TOP2201, an ongoing single-arm phase II trial evaluating the addition of the PCSK9 inhibitor alirocumab to anti-PD-1 therapy in patients with metastatic NSCLC who have experienced disease progression on prior immune checkpoint inhibitor-based regimens. The primary endpoint is objective response rate, with secondary endpoints assessing additional efficacy outcomes and safety. Findings from TOP2201 are expected to generate preliminary clinical and safety data on this combination strategy in the immunorefractory NSCLC setting.Clinical Trial Registration: www.clinicaltrials.gov identifier is NCT05553834.

Ifinatamab deruxtecan is a novel B7-H3-directed antibody-drug conjugate that leverages the clinically validated deruxtecan technology. We report dose-escalation results from a trial of ifinatamab deruxtecan in patients with solid tumours.

Lutetium-177 [177Lu]-prostate-specific membrane antigen (PSMA)-617 improves overall survival and progression-free survival in metastatic castration resistant prostate cancer (mCRPC), whereas immune checkpoint inhibitors (ICIs) have limited activity. Preclinical evidence suggests radioligand therapy might induce immunogenic cell death that can be enhanced with ICIs. This study evaluates the activity and adverse event profile associated with multiple doses of [177Lu]Lu-PSMA-617 with pembrolizumab.

[177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 (177Lu-PSMA-617) is a novel treatment for metastatic castration-resistant prostate cancer. Here, we aimed to evaluate 177Lu-PSMA-617 in patients with PSMA-expressing oligometastatic hormone-sensitive prostate cancer (HSPC).

Fulzerasib, a KRASG12C inhibitor, has shown clinical activity in previously treated non-small-cell lung cancer (NSCLC). Clinical studies indicate that combining a KRASG12C inhibitor with an anti-EGFR antibody is effective in colorectal cancer; however, its benefit in NSCLC remains to be explored.

Background: From 2019 July 15 to 2022 February 14, the REZOR study enrolled 369 treatment-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations (exon 19 deletion or L858R mutation). Patients were randomly assigned 1:1 to receive either rezivertinib (180 mg/d) plus gefitinib placebo or gefitinib (250 mg/d) plus rezivertinib placebo. Previous results demonstrated significantly improved progression-free survival (PFS) with rezivertinib versus gefitinib and a favorable safety profile. Here, we update the analyses of central nervous system (CNS) outcomes in patients with baseline CNS metastases. Methods: All patients underwent brain magnetic resonance imaging at baseline and each subsequent efficacy evaluation until radiological disease progression or any other treatment discontinuation criteria were met. EGFR mutation status was determined by testing using tissue or plasma samples during screening. Patients with stable, asymptomatic CNS metastasis were eligible for enrollment. The CNS full analysis set (cFAS) comprised patients with baseline CNS metastasis identified on magnetic resonance imaging and evaluated by blinded independent central review according to the Response Assessment in Neuro-Oncology Brain Metastases criteria. Patients with measurable CNS target lesions formed the CNS evaluable-for-response set (cEFR). Results: As of the 2023 November 30 data cutoff, 159 patients had baseline CNS metastasis in the cFAS (rezivertinib: n = 81; gefitinib: n = 78) and 25 in the cEFR (rezivertinib: n = 12; gefitinib: n = 13) per blinded independent central review. In the cFAS, 59 CNS PFS events occurred (rezivertinib: n = 30; gefitinib: n = 29). Median CNS PFS was significantly longer with rezivertinib (24.9 months; 95% confidence interval [CI], 16.5 months-not estimable [NE]) than with gefitinib (15.2 months; 95% CI, 10.5 months-NE), with a hazard ratio of 0.58 (95% CI, 0.34 to 0.99; P = 0.047). In the cEFR, the CNS objective response rate was 83.3% (95% CI, 51.6% to 97.9%) with rezivertinib and 76.9% (95% CI, 46.2% to 95.0%) with gefitinib (odds ratio = 1.50; 95% CI, 0.20 to 11.0; P = 0.690). No new safety findings were observed. Conclusions: Rezivertinib demonstrated a statistically significant superior CNS efficacy over gefitinib as first-line treatment in advanced EGFR-mutated non-small cell lung cancer patients with baseline CNS metastases. The safety profile was consistent with previous analyses. Trial registration: NCT03866499 (ClinicalTrials.gov).

Head and neck cancers (HNC) significantly impact patients' quality of life (QOL), with oral health often being significantly compromised, especially in advanced stages. Green tea, with its known anti-inflammatory and antioxidant properties, may help to improve oral health in these patients. Therefore, this study aims to investigate the effect of green tea-based mouth rinse on oral health status, pain, and QOL of advanced HNC patients.

To determine the pre-specified long term efficacy (survival and swallowing function) and safety of medial retropharyngeal lymph node (MRLN) region sparing radiotherapy for non-metastatic nasopharyngeal carcinoma.

Combination therapy with immune checkpoint inhibitors (ICIs) and chemotherapy has reshaped metastatic gastric cancer (GC) treatment, improving response rate, progression-free survival, and overall survival. We aimed to explore circulating immune cells and elucidate the mechanisms underlying the therapeutic effects of pembrolizumab and capecitabine/oxaliplatin (XELOX) in patients with metastatic GC. Potential immune mechanisms in GC tumors were retrospectively examined among patients from our phase 2 chemoimmunotherapy trial. Peripheral blood samples from patients with GC undergoing first-line pembrolizumab plus XELOX therapy were monitored using high-dimensional cytometry. Matched paired-tissue single-cell RNA-seq data were analyzed. Samples were collected from 24 patients at baseline, after one cycle of XELOX (FU1), and 18 weeks after pembrolizumab addition (FU2). Natural killer cell (CD3-NCAM +) and myeloid cell (CD11c + or CD14 +) subsets increased during chemoimmunotherapy.-At FU1, the proportion of PBMC monocytes was significantly higher in responders compared to non-responders. Consistent with the increase in monocyte-derived macrophages (M1-like) in paired tissues, monocytes in peripheral blood mononuclear cells increased at FU1. Immunosenescence score revealed recently mobilized monocytes infiltrating the tumor bed after chemotherapy. Gene expression analysis showed significantly upregulated CXCL8, CCL3, and CCL4 in FU1 responders. Early elevation of circulating monocytes correlated with better survival. After adding pembrolizumab, memory CD8 (CD3 + CD8 + CD27 + CD28 + CD45RO +) T cells increased in responders compared to non-responders. Our results elucidate the serial immunological landscape underpinning favorable responses to first-line ICI plus chemotherapy in patients with gastric cancer. Early distinct changes in blood myeloid cells during chemotherapy can be used to assess clinical response.

Although radical perineal prostatectomy is performed less frequently, it represents a minimally invasive open approach that avoids the retropubic space and extensive pelvic dissection. Its longterm oncologic and functional equivalence to standard retropubic prostatectomy has not been adequately evaluated in randomized cohorts.

DHP107 is an oral paclitaxel enabling administration of paclitaxel without Cremophor EL, a vehicle used to improve the solubility of intravenous (IV) paclitaxel. The randomized phase II OPERA study investigated the efficacy and safety of DHP107 versus IV paclitaxel in patients with HER2-negative breast cancer.

Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy can lessen side effects from treatment and are currently the standard of care for locally advanced head and neck cancer (LAHNC). The boost radiation can be delivered as a sequential or simultaneous integrated boost. Whether they differ in improving locoregional control or toxicity is largely unknown. In the current study, we prospectively compared two types of IMRT for non-nasopharyngeal LAHNC: sequential IMRT (SEQ-IMRT) and simultaneous integrated boost IMRT (SIB-IMRT).

While probiotics show promise in reducing chemoradiotherapy side effects like oral mucositis in head and neck cancer patients, robust clinical evidence of their consistent effectiveness is still needed. The objectives of this study were to compare the incidence and severity of oral mucositis, dysphagia, and compliance of radiotherapy treatment between the study arm (oral probiotics, along with concurrent chemoradiotherapy) and the control arm (concurrent chemoradiotherapy alone) in patients of locally advanced carcinoma oropharynx.

Breast cancer is the most common cancer among women. Surgical resection of the breast mass could induce an inflammatory response, which increases cytokines, such as interleukin IL beta-1 and IL-6. These mediators lead to peripheral and central sensitization and induce hyperalgesia. In this study, we hypothesized that perioperative lidocaine infusion could not only reduce serum interleukin levels but also reduce postoperative pain severity.

Loss of appetite and weight loss are major concerns in patients with pancreatic cancer. The aim of this study was to evaluate the associations of corticosteroid therapy with weight change and appetite in the long term, in patients with advanced pancreatic cancer.

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.

Despite adjuvant systemic chemotherapy after surgical resection in patients with pT4 stage colon cancer, a high percentage of them will develop peritoneal metastases. Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option with the goal of preventing metachronous peritoneal metastases. The aim of this study was to report the longer-term outcomes of peritoneal control with the use of intraoperative HIPEC based on mitomycin C after the last enrolled patient of the HIPECT4 trial reached 36 months follow-up.

Biliary tract cancer (BTC) is an aggressive malignancy characterized by a high recurrence rate and poor postoperative prognosis, despite advances in adjuvant therapy. This phase II study evaluated the efficacy and safety of a novel adjuvant regimen combining envafolimab, lenvatinib, and capecitabine in patients with BTC at high risk of recurrence following R0 resection.

A Japanese phase 2 trial of encorafenib plus binimetinib met the primary endpoint of the centrally assessed objective response rate in patients with unresectable BRAF V600E-mutated thyroid cancer. Consequently, encorafenib plus binimetinib has been approved in Japan. We present the health-related quality of life (HR-QoL) outcomes from the trial.