Treatment-related Adverse Events Research Articles

Effectiveness and Safety of Immune Checkpoint Inhibitors in Colorectal Cancer: A Systematic Review of Real-World Studies.

Immune checkpoint inhibitors (ICIs) have demonstrated significant efficacy in the treatment of colorectal cancer (CRC). However, most evidence has come from clinical trials with strict eligibility criteria. Understanding real-world effectiveness and safety of ICIs in CRC is important to guide routine clinical practice across diverse populations. A systematic review following PRISMA guidelines was conducted to identify observational studies evaluating ICI-based regimens compared to conventional or combination therapies in patients with CRC. Three databases (MEDLINE, Embase, and Scopus) were searched from inception through March 15, 2025. Eligible studies reported at least one efficacy outcome (e.g., progression-free survival [PFS], overall survival [OS], etc.) and/or safety outcome (e.g., adverse events) among real-world populations with CRC treated with ICIs. Study quality was assessed using the Newcastle-Ottawa Scale, and a narrative synthesis was performed to summarize the key findings. Eleven real-world studies met the inclusion criteria, encompassing data from 2,049 patients. In MSI-H/dMMR metastatic CRC, real-world findings aligned with the survival benefits observed in clinical trials, demonstrating improved PFS and OS compared to conventional therapies. For MSS/pMMR metastatic CRC, combining ICIs with other agents (e.g., tyrosine kinase inhibitors or chemotherapy) showed improvements but yielded conflicting results. Overall, the safety profiles were comparable to conventional therapies, with treatment-related adverse events occurring at similar rates. Real-world evidence supports the efficacy of ICI monotherapy in MSI-H/dMMR metastatic CRC and suggests potential benefits of ICI-based combination therapies in MSS/pMMR metastatic CRC. However, most of the data are derived from small, single-center cohorts, which limit their generalizability. Further multi-center studies are needed, especially to assess the efficacy of ICI-based combination therapies in the broader CRC population.

Safety and Efficacy of KN046 in Combination with KN026 in Patients with Advanced HER2-Positive Breast Cancer: A Phase II Trial

Abstract Purpose: In this study, we report the results from a phase II trial assessing the safety and efficacy of KN046 in combination with KN026 in patients with HER2-positive metastatic breast cancer, who had progressed after prior anti-HER2 combination therapies. Patients and Methods: Female patients with metastatic HER2-positive breast cancer, who were previously treated with at least one line of HER2-targeted combination therapy, were enrolled from multiple academic hospitals in China to receive KN046 (i.v. 5 mg/kg every 3 weeks) plus KN026 (i.v. 30 mg/kg every 3 weeks) until progression, unacceptable toxicities, or patient withdrawal. Efficacy was evaluated every 6 weeks per RECIST 1.1. The primary endpoint was objective response rate. Results: A total of 36 patients with the median age of 53 years were enrolled. Of these 36 patients, 30 (83.3%) received ≥3 lines of HER2-targeted combination therapies in the metastatic setting. Thirty-three patients were evaluable for overall response and all 36 for safety. The objective response rate was 47.2% (95% confidence interval, 30.4–64.5), with two patients achieving complete response. The median progression-free survival was 5.6 months (95% confidence interval, 4.1–13.8). Of the 36 patients, 34 (94.4%) experienced treatment-related adverse events (TRAE) of any grade, and 10 of 36 (27.8%) patients had experienced ≥grade 3 TRAEs. The most common TRAEs were infusion-related reaction (36.1%), rash (16.7%), alanine aminotransferase increased (13.9%), diarrhea (13.9%), and pruritus (13.9%). No treatment-related deaths were observed. Conclusions: The combination of KN046 and KN026, as a chemo-free regimen, demonstrated favorable clinical efficacy with comparative toxicities in pretreated patients with advanced HER2-positive breast cancer.

Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia.

This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC). A safety cohort received Gem 1,000 mg/m2 and Nab 125 mg/m2 on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15). Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group (P = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% v 7.0%, P = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab (P < .001). Gem/Nab/Toc decreased muscle loss versus Gem/Nab, with median change +0.1013% versus -3.430% (P = .0012) at 2 months and +0.7044 versus -3.353% (P = .036) at 4 months. Incidence of muscle loss was 43.48% on Gem/Nab/Toc versus 73.52% on Gem/Nab at 2 months (P = .0045) and 41.82% versus 68.75% (P = .0062) at 4 months. GDF15 was not changed by Gem/Nab or Gem/Nab/Toc. Although the primary end point was not met and TrAEs were increased by Toc, increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy.

Neoadjuvant chemotherapy with albumin-bound paclitaxel plus cisplatin and capecitabine for locally advanced esophageal squamous cell carcinoma: a phase 2 clinical trial.

Neoadjuvant chemotherapy with albumin-bound paclitaxel plus cisplatin and capecitabine for locally advanced esophageal squamous cell carcinoma: a phase 2 clinical trial.

Efficacy and safety of mitoxantrone hydrochloride liposome-containing regimens in treating refractory/relapsed acute myeloid leukemia

BackgroundDespite the poor prognosis for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML), an optimal treatment strategy remains undefined. Mitoxantrone (MIT) is widely used to treat R/R AML.MethodsThis prospective, single-center, open-label study assessed the efficacy and toxicity of mitoxantrone hydrochloride liposome (Lipo-MIT)-containing regimen therapy, intensified by adding cytarabine (Ara-C), cyclophosphamide (CTX) or other agents. The primary endpoint was composite complete remission (CRc), including complete remission (CR), complete remission with incomplete count recovery (CRi), and morphologic leukemia-free state (MLFS). The secondary endpoints included overall response rate (ORR), event-free survival (EFS), overall survival (OS), and safety.ResultsWe enrolled 20 patients (median, 38.50 years; range, 20.00–53.00 years) and treated them with a Lipo-MIT-containing regimen from April 29, 2022, to July 11, 2023. Twelve patients (60.00%) achieved CRc after one course of induction therapy, of which MAC (Lipo-MIT, Ara-C, CTX)-based regimen was the most commonly used (12/20, 60.00%) with a CRc rate of 66.67% (8/12). Additionally, 13 patients relapsed after allogeneic stem cell transplantation (allo-HSCT) with a CRc of 69.20% (9/13). The median follow-up time was 6.64 months, with a median OS of 9.99 months (range, 1.64–19.61; 95% confidence interval [CI], 2.05–17.92). Moreover, 95% patients experienced grade 3/4 hematologic treatment-related adverse events (TRAEs), including anemia (60.0%), thrombocytopenia (60.0%), leukopenia (65.0%), and neutropenia (55.0%). All patients experienced nonhematologic TRAEs, with 14 patients showing grade 3/4 toxicity.ConclusionThe Lipo-MIT-based regimens demonstrate preliminary efficacy in R/R AML, particularly in those who relapsed after allo-HSCT, though hematologic toxicity warrants careful monitoring.Clinical Trial Registration: Clinicaltrials.gov Identifier: NCT04645199 in November 27, 2020.

Anlotinib Plus Docetaxel is Promising in Advanced NSCLC Progressing on First-Line Immunotherapy: A Pooled Analysis of Two Randomized Trials.

Therapeutic options for patients with advanced non-small cell lung cancer (NSCLC) after progression on immune checkpoint inhibitors (ICIs) remain a significant challenge. This analysis compared outcomes of anlotinib plus docetaxel versus docetaxel alone in this population using the pooled data from two prospective randomized trials (ALTER-L016; ALTER-L018). Adult patients with EGFR/ALK/ROS1 wild-type advanced NSCLC progressing on first-line ICIs were eligible. Patients were randomly assigned to anlotinib plus docetaxel or docetaxel alone. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Seventy-one patients were included in this pooled analysis (L016, n = 39; L018, n = 32), of whom, 40 received anlotinib plus docetaxel and 31 received docetaxel. The median follow-up of all patients was 27.0months. The median PFS was longer with anlotinib plus docetaxel than with docetaxel alone (5.4months [95% CI 5.0-9.3] vs. 2.3months [95% CI 1.4-2.9]; hazard ratio [HR], 0.34; 95% CI 0.18-0.63; P < 0.001). Both ORR (25.0% vs. 12.9%) and DCR (82.5% vs. 45.2%) were higher in the anlotinib plus docetaxel group than in the docetaxel group. Median OS was 16.2months (95% CI 8.3-21.3) with anlotinib plus docetaxel versus 13.7months (95% CI 4.6-22.3) with docetaxel (HR = 0.82; 95% CI 0.47-1.44; P = 0.488). Subsequent ICI therapy was associated with a longer OS. Grade 3 treatment-related adverse events occurred in 32.5% of patients receiving anlotinib plus docetaxel and 6.5% of patients receiving docetaxel. Anlotinib plus docetaxel improved PFS but not OS versus docetaxel in patients with advanced NSCLC progressing on ICIs. Larger standardized phase 3 trials are needed to verify these findings. ALTER-L016 (ClinicalTrials.gov identifier, NCT03726736). ALTER-L018 (ClinicalTrials.gov identifier, NCT03624309).

Phase II study of venetoclax added to bendamustine and obinutuzumab in patients with high-risk follicular lymphoma as front-line therapy: PrE0403

Over-expression of BCL-2 defines follicular lymphoma (FL). Venetoclax (VEN), a selective BCL-2 inhibitor, has previously been evaluated with bendamustine-based chemoimmunotherapy. VEN was given continuously, resulting in promising efficacy but unacceptable toxicity. The Phase II PrE0403 study was designed to evaluate intermittent dosing of VEN (10 days per cycle) combined with obinutuzumab and bendamustine (VEN-OB) in untreated FL subjects with high-risk features defined as a FLIPI-1 score of ≥3 and/or high tumor burden by GELF criteria. A total of 56 subjects were planned to be accrued with a goal of having 51 subjects eligible to improve the historical 50% CR rate to 65% with an 85% power and 15% type I error rate. Immunohistochemistry (IHC) expression of 3 antiapoptotic proteins (BCL-xL, MCL-1, and BCL-2) was performed and correlated with clinical outcomes. All 56 subjects were eligible and treated. CR rate was 41/56 (73.2%) and ORR was 52/56 (92.5%) meeting the primary endpoint. 2-year estimated PFS was 87.5% (90% CI: 75.3,93.9%) and 2-year estimated OS was 94.6% (90% CI: 86.7, 97.9%). However, the incidence of treatment-related adverse events ≥ grade 3 was 83.9% and serious adverse events were seen in 57.1%. After induction, atypical infections, including Grade 5 events, occurred. Anti-apoptotic protein expression by IHC was not correlated with clinical outcomes. Thus, while meeting the primary efficacy end point, VEN-OB is considered overly toxic in high-risk FL.

The Composite Digital Therapeutic Index (cDTI): A Multidimensional Framework and Proof-of-Concept Application to FDA-Authorized Treatments.

Introduction Prescription digital therapeutics (PDTs) are an emerging class of regulated software-based interventions with increasing FDA authorizations. However, there is no standardized framework to evaluate and benchmark their overall therapeutic value. We aimed to develop and validate a Composite Digital Therapeutic Index (cDTI) framework. This proof-of-concept application integrates efficacy, engagement, quality of evidence, and safety profile from registrational trials to compare PDTs using publicly available regulatory summaries, registries, and study readouts. Methods We developed a scoring framework incorporating four domains (efficacy, engagement, evidence quality, and safety), each quantified and combined into a composite index. Efficacy was calculated using standardized mean difference (SMD; Hedges' g) adjusted for statistical significance. Engagement was based on the mean proportion of patients achievingtherapeutic module completion. Evidence quality was graded using an adapted American Academy of Neurology Class of Evidence framework. Safety was assessed based on treatment-emergent adverse events (TEAEs) using a hierarchical penalty system. In a proof-of-concept application of the framework, we applied cDTI to two FDA-cleared first- and second-generation PDTs, reSET-O for opioid use disorder (Pear Therapeutics, Boston, MA, USA) and CT-132 for episodic migraine (Click Therapeutics, New York, NY, USA), respectively. Results CT-132 achieved a cDTI score of 0.296, substantially (1287%) higher than reSET-O, which scored 0.023. CT-132's superior performance was driven by a statistically significant efficacy outcome (adjusted SMD 0.33), high engagement (89.7%), Class I evidence quality with sham and double-blind, and no treatment-related adverse events. In contrast, reSET-O showed a non-significant primary outcome (adjusted SMD 0.0895), moderate engagement (63.0%), Class III evidence quality without patient blind and usual-care control, and missing systematic safety reporting requiring a conservative penalty. Discussion The cDTI successfully differentiated the overall therapeutic profiles of two PDTs across multiple clinical and usability domains. This multidimensional approach highlights how digital therapeutics with similar regulatory status can differ meaningfully in trial quality, efficacy, engagement, and safety. The cDTI offers a transparent, reproducible method for comparing PDTs and may aid stakeholders including providers, payers, regulators, and patients in decision-making about digital therapeutic adoption and coverage. Conclusion The cDTI provides a reproducible framework to evaluate PDTs based on clinical, usability, and safety parameters. Future work aims to expand the framework across all FDA-cleared PDTs and explore incorporation of real-world effectiveness, equity, and cost-effectiveness domains.

Radiotherapy, tyrosine kinase inhibitors, immune checkpoint inhibitors combined with hepatic arterial infusion chemotherapy of RALOX versus FOLFOX for hepatocellular carcinoma with portal vein tumor thrombus: a propensity score-matching cohort study

BackgroundThis retrospective study aimed to evaluate the safety and effectiveness of hepatic arterial infusion chemotherapy with raltitrexed and oxaliplatin (RALOX-HAIC) combined with radiotherapy, tyrosine kinase inhibitors, and immune checkpoint inhibitors in patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).MethodsA propensity score-matching (PSM) cohort study was conducted. The tumor response, treatment-related adverse events, survival outcomes were compared. Univariate and multivariate analyses were conducted to explore the risk factors of overall survival (OS).ResultsTwenty-one pairs of patients were evaluated after PSM. No statistical differences were found in the tumor response, objective response rate, disease control rate, PVTT response, surgical resection rate, metastasis, and mortality between the two groups before and after PSM. Compared with the FOLFOX-HAIC group, the incidences of abdominal pain and fever was lower in the RALOX-HAIC group (P = 0.028, P = 0.029). These differences still had statistical significance after PSM (P = 0.013, P = 0.014). No statistical differences were found in OS and progression-free survival (PFS) between the two groups before and after PSM (Before [OS: hazard ratio(HR) = 1.138; 95%CI 0.569–2.276, P = 0.715; PFS: HR = 0.549; 95%CI 0.195–1.548, P = 0.257; After [OS: HR = 0.998; 95%CI 0.438–2.274, P = 0.995; PFS: HR = 0.792; 95%CI 0.359–1.748, P = 0.564]). The prealbumin < 170 mg/L before therapy was an independent risk factor for OS (HR = 2.234; 95%CI 1.051–4.751; P = 0.037).ConclusionsThe RALOX-HAIC combined radiotherapy, TKI, and ICI may provide similar survival advantages with fewer treatment-related abdominal pain and fever compared to FOLFOX-HAIC for HCC patients with PVTT. The prealbumin < 170 mg/L before therapy is an independent risk factor for OS.

Efficacy and safety of neoadjuvant systemic therapy in resectable hepatocellular carcinoma: a Systematic Review and meta-analysis

BackgroundNeoadjuvant systemic therapy has been shown to benefit patients with solid tumors such as breast cancer and colorectal cancer, but its application in hepatocellular carcinoma (HCC) is still in the exploratory stage, with no established effective regimen. This systematic review and meta-analysis aims to investigate the efficacy and safety of neoadjuvant systemic therapy in patients with resectable HCC.MethodsThe clinical trials of resectable HCC neoadjuvant systemic therapy in PubMed, Embase and the Cochrane Library were systematically searched. A meta-analysis was performed using STATA/MP18.0 software, and the effect size was calculated using either a fixed effects model or a random effects model, and 95% confidence intervals (CIs) were calculated. Subgroup analysis was performed according to the neoadjuvant systemic therapy regimen.ResultsThis meta-analysis included 328 patients from 15 studies. In patients with resectable HCC, the pooled pathologic complete response (pCR) rate was 15% (95%CI: 10%–21%), the major pathologic response (MPR) rate was 28% (95%CI: 21%–35%), the incidence of grade 3–4 treatment-related adverse events (TRAEs) was 11% (95% CI: 4%–20%), the objective response rate (ORR) was 27% (95% CI: 20%–35%), the surgical resection rate was 84% (95%CI: 75%–92%), and the delay rate was 0.00% (95% CI: 0%–4%). The results of subgroup analysis showed that the efficacy of targeted therapy combined with immunotherapy is superior to dual ICI (immune checkpoint inhibitor) combination therapy and ICI monotherapy, while the safety of the ICI monotherapy was the highest, superior to the dual ICIs and the targeted therapy combined with immunotherapy.ConclusionNeoadjuvant systemic therapy shows preliminarily beneficial outcomes in resectable HCC treatment. However, future large-scale and multicenter randomized controlled trials are needed to confirm this conclusion.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024562257

A COMPARATIVE EVALUATION OF PHOSPHODIESTERASE-5 INHIBITORS IN ERECTILE DYSFUNCTION TREATMENT: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS OF DOUBLE-BLINDED, PLACEBO-CONTROLLED, RANDOMIZED TRIALS

A COMPARATIVE EVALUATION OF PHOSPHODIESTERASE-5 INHIBITORS IN ERECTILE DYSFUNCTION TREATMENT: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS OF DOUBLE-BLINDED, PLACEBO-CONTROLLED, RANDOMIZED TRIALS

EARLY CLINICAL DEVELOPMENT PROGRAM, INCLUDING RESULTS OF A FIRST-IN-HUMAN TRIAL OF LIB-01, A NOVEL, FIRST IN CLASS POTENTIAL ORAL ERECTILE DYSFUNCTION DRUG WITH UNIQUE PHARMACODYNAMIC PROPERTIES

EARLY CLINICAL DEVELOPMENT PROGRAM, INCLUDING RESULTS OF A FIRST-IN-HUMAN TRIAL OF LIB-01, A NOVEL, FIRST IN CLASS POTENTIAL ORAL ERECTILE DYSFUNCTION DRUG WITH UNIQUE PHARMACODYNAMIC PROPERTIES

Hepatic artery infusion of FOLFOX chemotherapy plus camrelizumab combined with sorafenib for advanced hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage C (Double-IA-001): a phase II trial

BackgroundHepatic arterial infusion chemotherapy (HAIC) with a combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown excellent local control for patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). In China, both camrelizumab (a programmed cell death-1 [PD-1] inhibitor) and sorafenib have been approved for the first-line treatment of advanced HCC. This study aimed to investigate the efficacy and safety of hepatic artery infusion of FOLFOX chemotherapy plus camrelizumab combined with sorafenib in BCLC stage C advanced HCC.MethodsThis was a single-arm phase II trial (ChiCTR2100041874) with a Simon’s two-stage design. Eligible patients were given a maximum of 6 cycles of hepatic artery infusion with FOLFOX chemotherapy plus camrelizumab (200 mg once every 3 weeks). Sorafenib (400 mg orally twice daily) was given since day 3 after the completion of the first cycle of hepatic artery infusion until disease progression, intolerable toxicity, or conversion to surgical resection. The primary endpoint was objective response rate (ORR) based on the modified Response Evaluation Criteria In Solid Tumors (mRECIST).ResultsBetween January 4, 2021, and December 11, 2023, 25 patients were enrolled. Eleven patients had partial response, with an ORR of 44.0% (95% CI, 24.6–63.5%). The primary endpoint was not met, and the study failed to enter the second stage. Median progression-free survival was 4.87 months (95% CI, 2.07–7.66), with a 12-month rate of 23.2%. Median overall survival was 8.87 months (95% CI, 8.17–9.57), with 12- and 24-month rates of 40.3% and 26.9%, respectively. Two (8.0%) patients received curative resection after the study treatment. Grade ≥ 3 treatment-related adverse events occurred in 19 (76.0%) patients, with the most common being decreased lymphocyte count (13 [52.0%]), increased aspartate aminotransferase (11 [44.0%]), and increased alanine aminotransferase (seven [28.0%]).ConclusionsHepatic artery infusion of FOLFOX chemotherapy plus camrelizumab combined with oral sorafenib shows manageable safety profile but modest antitumor activity in patients with BCLC stage C advanced HCC.

Atezolizumab plus personalized neoantigen vaccination in urothelial cancer: a phase 1 trial.

Features of constrained adaptive immunity and high neoantigen burden have been correlated with response to immune checkpoint inhibitors (ICIs). In an attempt to stimulate antitumor immunity, we evaluated atezolizumab (anti-programmed cell death protein 1 ligand 1) in combination with PGV001, a personalized neoantigen vaccine, in participants with urothelial cancer. The primary endpoints were feasibility (as defined by neoantigen identification, peptide synthesis, vaccine production time and vaccine administration) and safety. Secondary endpoints included objective response rate, duration of response and progression-free survival for participants treated in the metastatic setting, time to progression for participants treated in the adjuvant setting, overall survival and vaccine-induced neoantigen-specific T cell immunity. A vaccine was successfully prepared (median 20.3 weeks) for 10 of 12 enrolled participants. All participants initiating treatment completed the priming cycle. The most common treatment-related adverse events were grade 1 injection site reactions, fatigue and fever. At a median follow-up of 39 months, three of four participants treated in the adjuvant setting were free of recurrence and two of five participants treated in the metastatic setting with measurable disease achieved an objective response. All participants demonstrated on-treatment emergence of neoantigen-specific T cell responses. Neoantigen vaccination plus ICI was feasible and safe, meeting its endpoints, and warrants further investigation. ClinicalTrials.gov registration: NCT03359239 .

Zanidatamab monotherapy or combined with chemotherapy in HER2-expressing gastroesophageal adenocarcinoma: a phase 1 trial

There is a need for novel therapies for patients with previously treated HER2-positive gastroesophageal adenocarcinoma (GEA). This phase 1 (NCT02892123) dose-escalation and expansion trial evaluated zanidatamab (a dual HER2-targeted bispecific antibody) ± chemotherapy in previously treated patients with HER2-expressing, locally advanced/metastatic cancers. Here, we report the outcomes for GEA cohorts receiving zanidatamab monotherapy or with chemotherapy (paclitaxel or capecitabine). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rate (ORR), disease control rate, progression-free survival, pharmacokinetics, and immunogenicity. Seventy patients were enrolled (n = 29 monotherapy; n = 41 combination therapy); most received prior HER2-targeted agents (monotherapy, 93%; combination therapy, 95%). With monotherapy, 69% of patients had any-grade treatment-related AEs (TRAEs); 17% had grade ≥ 3 TRAEs. The most common any-grade TRAEs were diarrhea (41%) and infusion-related reactions (24%). With combination therapy, 98% of patients had any-grade TRAEs; 51% had grade ≥ 3 TRAEs. The most common any-grade TRAEs were diarrhea (68%) and fatigue (44%). Confirmed ORR was 32.1% (95% confidence interval [CI] 15.9–52.4) with monotherapy and 48.6% (95% CI 31.9–65.6) with combination therapy. In heavily pre-treated patients with HER2-expressing GEA, zanidatamab ± chemotherapy had a manageable safety profile and promising antitumor activity.

Outcomes of Radium-223 and Stereotactic Ablative Radiotherapy Versus Stereotactic Ablative Radiotherapy for Oligometastatic Prostate Cancers: The RAVENS Phase II Randomized Trial.

Randomized clinical trials (RCTs) have shown progression-free survival (PFS) benefits of metastasis-directed therapy (MDT) without androgen deprivation therapy for oligometastatic castration-sensitive prostate cancer (omCSPC). Most patients with bone metastatic (BM) omCSPC recur with additional bone disease after MDT. We hypothesized the BM-targeting alpha-emitter radium-223 dichloride (Ra223) could target subclinical bone disease and delay progression. This is an investigator-initiated, multicenter, open-label phase II RCT. Eligible men with recurrent omCSPC with ≥one bone metastasis (≤three on conventional imaging and/or ≤five on molecular imaging) were randomly assigned (1:1) to stereotactic ablative radiation (SABR) MDT alone or SABR MDT with Ra223 (six cycles). Primary end point was composite PFS. From August 9, 2019, to March 2, 2023, 64 patients were randomly assigned, 33 to SABR MDT and 31 to SABR MDT/Ra223 balancing for key covariates. Most SABR MDT/Ra223 patients (87%) received six cycles of Ra223. The median PFS was 11.8 months with SABR MDT and 10.5 months with SABR MDT/Ra223 (adjusted hazard ratio [aHR], 1.42 [95% CI, 0.79 to 2.56]; P = .24). Seven patients (11%) experienced grade 3 treatment-related adverse events (no grade 4 or 5), 2 of 33 (6%) with SABR and 5 of 30 (17%) with SABR MDT/Ra223. Patients with high-risk (HiRi) pathogenic mutations in ATM, BRCA1/2, RB1, or TP53 had worse PFS (HR, 5.95 [95% CI, 1.83 to 19.3]; P = .003). Greater T-cell receptor (TCR) unique productive rearrangements were prognostic for improved PFS independent of the treatment arm (aHR, 0.45 [95% CI, 0.21 to 0.96]; P = .04). Adding Ra223 to SABR MDT in BM omCSPC does not delay progression of disease. We provide evidence for an HiRi mutational signature and TCR repertoire as prognostic biomarkers in omCSPC treated with SABR MDT, highlighting the importance of collecting biological correlates in RCTs for omCSPC.

Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study.

Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study.

Hepatic artery infusion chemotherapy combined with camrelizumab and apatinib as conversion therapy for patients with unresectable hepatocellular carcinoma: a single-arm exploratory trial

BackgroundThe development of systemic therapy, including targeted drugs and immune checkpoint inhibitors, has significantly improved the prognosis of patients with advanced unresectable hepatocellular carcinoma (uHCC). Hepatic arterial infusion chemotherapy (HAIC) has been gradually applied to the treatment of advanced uHCC, showing good potential as conversion therapy. We aimed to investigate the efficacy and safety of HAIC combined with camrelizumab and apatinib as conversion therapy for uHCC.MethodsThis study was a single-arm exploratory trial (NCT05099848) in patients with uHCC. Eligible patients received apatinib 250 mg once daily, camrelizumab 200 mg on day 3, and HAIC with FOLFOX regimen (oxaliplatin 85 mg/m2 at hours 0–2, leucovorin 400 mg/m2 at hours 2–3, and fluorouracil 400 mg/m2 at hour 3, followed by fluorouracil 2400 mg/m2 for 46 h) on days 4–5 of each 21-day cycle for up to 8 cycles. Primary endpoints were conversion rate and margin-free (R0) resection rate.ResultsBetween March 2021 and July 2023, 19 patients were enrolled. Median follow-up was 14.9 months (interquartile range, 10.9–21.1). Disease became resectable in 14 (73.7%) of 19 patients; nine (47.4%) patients received R0 resection, while five (26.3%) refused surgery and opted for observation. Three (33.3%) of nine patients with surgery achieved major pathological response, including two (22.2%) with pathological complete response. Objective response and disease control rates were 47.4% (9/19) and 89.5% (17/19) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 and both 89.5% (17/19) per modified RECIST. Survival data were immature. Fourteen (73.7%) of 19 patients had grade 3 or higher treatment-related adverse events, with the most common being increased alanine aminotransferase or aspartate aminotransferase (seven [36.8%]) and increased lymphocyte count (six [31.6%]). No treatment-related deaths occurred.ConclusionsThe combination of HAIC, camrelizumab, and apatinib as conversion therapy shows promising clinical benefits and a manageable safety profile in patients with uHCC. Future randomized controlled trials are warranted.Trial registrationClinicalTrials.gov NCT05099848. Registered on October 13, 2021.

Efficacy of topical moxifloxacin on therapeutic laparoscopy-induced wound healing: a double-blind, randomized clinical trial

BackgroundWound healing is crucial for maintaining healthy skin and preventing complications. Topical administration is a preferred method for delivering therapeutic medicines at the surgery site, as it is simple, affordable, and does not result in systemic harm or antibiotic resistance. Moxifloxacin (MXF), a broad-spectrum antibiotic with anti-inflammatory effects, seems to be effective against bacteria and accelerates wound healing. This study aims to determine the therapeutic effect of topical MXF on wound healing after therapeutic laparoscopy.MethodsThis double-blind clinical trial involved 80 patients with therapeutic laparoscopy-induced wounds, randomly assigned to either 0.5% MXF cream or placebo, 24 h after surgery. The primary outcome was wound healing assessment using the REEDA index. Patients were followed by 1, 3, and 5 days of inclusion.ResultsOf the 80 study participants included, 50 were women (62.5%), with the mean (SD) age of the participants being 49.5 (19.8) years in the MXF group and 45.8 (17.8) years in the control group. The severity of redness, oedema, and discharge in the MXF group was significantly lower on the first, third, and fifth days of treatment. The case group showed a significant decrease in ecchymosis from the third day of treatment compared to the control group, and no significant difference was observed in wound approximation rate. Hence, topical MXF therapy yielded a significant decrease in REEDA index MXF (P-Value < 0.0001). No treatment-related serious adverse events occurred in the MXF group vs. the comparator group.ConclusionsThe results of the current clinical trial demonstrated that the use of topical MXF could be a potential option to expedite therapeutic laparoscopy-induced wound healing by reducing redness, oedema, ecchymosis, and discharge with a satisfactory safety profile.Trial registrationIRCT20181208041882N5, 25/10/2021 (https://en.irct.ir/trial/46768).

Real-world efficacy and tolerability of axitinib + pembrolizumab in the treatment of renal cell carcinoma.

Combination therapy with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKIs) is standard of care for metastatic renal cell carcinoma (mRCC); however, no head-to-head trials have compared FDA-approved regimens. This project aims to provide real-world data on the safety and efficacy of axitinib + pembrolizumab in the treatment of mRCC and describe management of common treatment-related adverse events. This is a retrospective, observational, quality improvement project conducted at the Robert H Lurie Comprehensive Cancer Center of Northwestern University in Chicago, Illinois. Patients 18 years of age or older with stage IV RCC who received axitinib + pembrolizumab between April 2019 and February 2024 were included. Endpoints included progression-free survival (PFS), overall survival (OS), duration of treatment, subsequent therapies, and safety outcomes. Thirty-one patients received axitinib + pembrolizumab for mRCC. With a median follow-up time of 22.6 months, PFS was 37.4 months and OS was not reached. Ninety-four percent of patients experienced a treatment-related adverse event with 32.3% classified as grade 3 or higher. Fifty two percent of patients required axitinib dose reductions, 70.9% had at least one axitinib dose held, and 70.9% had at least one pembrolizumab dose held. Patients with axitinib dose reductions demonstrated improved OS at one year (92.9% vs. 80%). This retrospective study corroborates the findings of the KEYNOTE-426 trial and further demonstrates the effectiveness of axitinib + pembrolizumab combination therapy in the treatment of mRCC. Dose reductions and holds do not appear to impact treatment efficacy.