Partial Response Research Articles

A Phase II Multi-Center Trial of Trabectedin in Combination with Olaparib in Patients with Advanced Unresectable or Metastatic Sarcoma.

Soft tissue sarcoma (STS) are rare malignancies with poor prognosis and limited systemic treatment options. We conducted a phase II study to assess the efficacy and safety of trabectedin and olaparib in patients with advanced disease. Patients with STS who received ≥ 1 prior therapy were recruited into two cohorts. Cohort 1 included leiomyosarcoma and liposarcoma; Cohort 2 included other histologies. All patients received trabectedin (1.1 mg/m2 24-hour infusion every 21 days) and olaparib (150 mg BID continuously). The study was conducted using a Simon Minimax two-stage design with a primary endpoint of objective response rate per RECIST 1.1. Twenty-nine patients enrolled (Cohort 1:16, Cohort 2:13); one patient in Cohort 2 was not evaluable. There were no confirmed objective responses in Cohort 1; best response was stable disease in 12 patients (75%) and progressive disease in 4 (25%). Two partial responses were observed in Cohort 2 (n=12). The most common adverse events were fatigue (75%), neutropenia (75%), anemia (68%), and thrombocytopenia (68%). Median progression free survival and overall survival for all patients was 3.5 (95% CI 3.3-8.2) and 13.2 months (95% CI 10.3-20.9), respectively. Next generation sequencing of 17 tumors revealed multiple abnormalities, most commonly in TP53, RB1, and ATRX. Trabectedin plus olaparib conferred high rates of toxicity and failed to demonstrate objective responses in leiomyosarcoma and liposarcoma. Preliminary evidence of clinical benefit in two patients in cohort 2 suggests potential value of either or both drugs in other sarcomas.

Impact of glucocorticoid tapering speed on renal outcomes in proliferative lupus nephritis: a multicentre retrospective study.

Recent guidelines and recommendations for lupus nephritis (LN) suggest rapid glucocorticoid (GC) reduction; however, robust supporting evidence remains limited. This study aimed to evaluate the impact of rapid GC reduction on renal outcomes in patients with proliferative LN. We conducted a multicentre retrospective chart review of patients with GC-naïve, biopsy-proven proliferative LN with available urinary protein-to-creatinine ratio (UPCR) data before and 52 weeks after GC treatment. Patients who reduced their prednisolone-equivalent dose to ≤ 7.5 mg/day within 6 months (rapid GC reducers) were compared with those who did not (conventional GC reducers) regarding partial renal response (PRR) at 12 months. Modified Poisson regression analysis was used to adjust for confounding factors. A total of 344 patients from 17 centres were included: 50 rapid GC reducers and 294 conventional GC reducers. PRR at 12 months was achieved by 43/50 (86%) in the rapid GC group and 248/294 (84.4%) in the conventional group. After adjusting for age, initial UPCR, initial estimated glomerular filtration rate, the presence of a concomitant membranous lesion in the glomerulus, initial GC dose, use of methylprednisolone pulse therapy, strong immunosuppressants (mycophenolate mofetil, cyclophosphamide, or rituximab), and hydroxychloroquine, no significant difference was observed in PRR at 12 months (adjusted risk ratio: 0.92, p= 0.758). Relapse rates and serious adverse events over 2 years of follow-up were also comparable between the groups. Rapid GC reduction to ≤ 7.5 mg/day within 6 months did not compromise renal outcomes or increase relapse in proliferative LN.

EORTC/ESTRO defined induced oligopersistence of liver metastases from colorectal cancer - outcomes and toxicity profile of computer tomography guided high-dose-rate brachytherapy

Colorectal cancer (CRC) often leads to liver metastases, which may be resistant to systemic therapy. This study assessed outcomes and toxicity of computed tomography (CT) guided high-dose-rate (HDR) brachytherapy (BRT) in oligopersistent liver metastases from CRC. The study included patients with liver metastases classified as EORTC/ESTRO-defined induced oligopersistence after multiple systemic therapy lines. Up to four persistent liver metastases per patient were treated with CT-guided brachytherapy (CT-BRT). Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The analysis focused on overall survival (OS), progression-free survival (PFS), tumor burden score (TBS), and the prognostic value of changes in metastasis size. Sixty-eight CRC patients were enrolled. During a median follow-up of 17 months, the median OS was 16 months, and the median PFS was 13 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were observed in 7%, 35%, 44%, and 6% of patients, respectively. Patients with an objective response (ORR) of 42% had longer OS and PFS than those without it. OS was affected by lymph node metastases and metastasis size reduction, while PFS was additionally influenced by the administered dose. Multivariate analysis showed OS was linked to lymph node metastases (p = 0.001) and ORR (p = 0.004), and PFS to tumor burden score (TBS) difference (p = 0.017) and post-CT-BRT single metastasis size (p = 0.026). CT-BRT for CRC oligopersistent liver metastases is effective, improving PFS and OS, with TBS difference identified as a key response parameter for future strategies.

Promising Response to Pyrotinib in Non-Small-Cell Lung Cancer with the Rare HER2 R456C Mutation: A Case Report.

HER2 exon 20 insertions exhibit relative resistance to chemotherapy and covalent HER2-targeted tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Furthermore, specific missense mutations in the extracellular domain of the HER2 protein have been identified as oncogenic drivers in NSCLC. However, their structural properties and clinical response to HER2-targeted inhibitors remain poorly understood, warranting further investigation. R456C represents a rare exon 12 missense mutation in the HER2 extracellular domain, with limited documentation in NSCLC. This study presents an atypical case of NSCLC with a HER2 R456C mutation, where the patient experienced a favorable response and substantial survival benefit from the HER2-targeted inhibitor pyrotinib. A patient, a 65-year-old man diagnosed with stage IIIB lung adenocarcinoma, initially underwent radical concurrent chemoradiotherapy. Upon disease recurrence, polymerase chain reaction assay detected no oncogenic alterations, and programmed cell death ligand 1 (PD-L1) expression was negative. Chemotherapy in combination with bevacizumab resulted in stable disease, providing a progression-free survival (PFS) benefit of 6 months. However, anlotinib proved ineffective against brain metastasis, necessitating brain radiotherapy. A subsequent lung biopsy confirmed adenocarcinoma and next-generation sequencing identified a somatic HER2 exon 12 missense mutation, p.R456C. Following pyrotinib administration, the patient's pulmonary metastases significantly diminished, and the brain metastasis regressed, resulting in a partial response and a PFS benefit of 13 months. To the best of our knowledge, this study represents the first reported case demonstrating the promising efficacy of pyrotinib in HER2-altered NSCLC harboring the ra-re exon 12 R456C mutation. Heterogeneous alterations in the HER2 extracellular segment, such as R456C, may be targetable and could confer survival benefits with HER2-targeted inhibitors.

Comparative Efficacy of Ciltacabtagene Autoleucel Versus Standard-of-Care Treatments for Patients with Previously Treated Relapsed or Refractory Multiple Myeloma: A Matching-Adjusted Indirect Comparison.

Matching adjusted indirect comparisons (MAICs) were performed to compare the efficacy of cilta-cel versus elotuzumab+pomalidomide+dexamethasone (EloPd), isatuximab+carfilzomib+dexamethasone (IsaKd), isatuximab+pomalidomide+dexamethasone (IsaPd), and selinexor+bortezomib+dexamethasone (SVd) in patients withrelapsed or refractory multiple myeloma (RRMM) who have received at least one prior therapy and are lenalidomide-refractory. Unanchored MAICs were performed using individual patient-level data (IPD) for all apheresed patients randomized to the cilta-cel arm of CARTITUDE-4 (n =208) and published arm-level data for EloPd from ELOQUENT-3 (n=60), IsaKd from IKEMA (lenalidomide-refractory subgroup, n=57), IsaPd from ICARIA-MM (n=154), and SVd from BOSTON (lenalidomide-refractory subgroup, n=53). Eligibility criteria from each comparator trial were applied to the cilta-cel arm IPD, and further imbalances in patient characteristics were adjusted by weighting the cilta-cel patient data to match the reported baseline characteristics of the comparator trials. Comparative efficacy was estimated for overall response rate, very good partial response or better (≥VGPR) rate, complete response or better (≥CR) rate, progression-free survival (PFS), and overall survival (OS). After adjustment, cilta-cel patients were significantly more likely to achieve an overall response versus EloPd, IsaPd, and SVd, and were significantly more likely to achieve≥VGPR and≥CR versus all comparators. Cilta-cel patients also had significant reductions in the risk of disease progression or death (PFS) versus all comparators: 64% versus EloPd, 49% versus IsaKd, 69% versus IsaPd, and 62% versus SVd. Similarly, cilta-cel patients had significant improvements in OS for all feasible comparisons: 52% versus EloPd, 58% versus IsaPd, and 60% versus SVd. Cilta-cel patients demonstrated clinically meaningful benefits over EloPd, IsaKd, IsaPd, and SVd for response and survival outcomes, highlighting its superiority over alternative treatment options for patients with RRMM who have received at least one prior therapy and are refractory to lenalidomide.

Real world study on efficacy and safety of surufatinib in advanced solid tumors evaluation

Surufatinib is a novel, China-developed small-molecule tyrosine kinase inhibitor that demonstrates high selectivity for VEGFR, FGFR1, and CSF1R. Surufatinib has been approved for the treatment of neuroendcrine tumors, including pancreatic neuroendocrine tumors (PNEN) and non-pancreatic neuroendocrine tumors (N-pNEN). The purpose of this retrospective study is to assess Surufatinib’s safety and effectiveness in patients with various advanced solid malignancies. The general clinical statistics and follow-up data of patients treated with Surufatinib for advanced solid tumors at Zhejiang Provincial People’s Hospital between January 2021 and April 2024 were gathered. Enhanced CT was used to assess the effectiveness during that time, and cases side effects were gathered. Survival rates of different diseases were analyzed using the Kaplan-Meier method. A total of 28 eligible patients were enrolled in this study. At the end of follow-up, treatment with Surufatinib resulted in the following outcomes: Complete response (CR) in 0 cases (0.0%), Partial response (PR) in 5 cases (17.9%), Stable disease (SD) in 7 cases (25.0%), and Progressive disease (PD) in 16 cases (57.1%). Objective response rate (ORR) and Disease control rate (DCR) were 17.9% and 42.9%, respectively. In the PNEN group, ORR was 33.3%, DCR was 66.7%, median progression-free survival (mPFS) was 11 months, while median overall survival (mOS) was 17 months. In the N-pNEN group, ORR was 14.3%, DCR was 42.3%, mPFS was 6 months and mOS was 7 months. ORR was 8.3%, DCR was 25%, mPFS was 2 months, and mOS was 2 months. The most common adverse reactions included hypoproteinemia, proteinuria, bone marrow suppression and gastrointestinal toxicity, and which of them were grade 1 to grade 2. In advanced solid tumors beyond PNEN, Surufatinib demonstrates clinically meaningful survival benefits for patients refractory to standard therapies, with a generally manageable safety profile.

Isolated Limb Infusion or Perfusion as First-Line Versus Second-Line Therapy for In-Transit MetastaticMelanoma.

In-transit metastases (ITM) develops in 10% of patients with high-risk melanoma. Isolated limb infusion and perfusion (ILI/ILP) are well-established therapies for ITM, but the ideal line of therapy has not been defined. This study compared ILI/ILP as first- versus second-line therapy. An international multi-institution retrospective study reviewed patients with unresectable ITM who underwent ILI/ILP from 2006 to 2023. The study was comprised of 364 patients (55% female) with a median age of 71 years. Of the 364 patients, 329 (90%) were treated with ILI/ILP as first-line therapy, and 35 (10%) were treated with ILI/ILP as second-line therapy. The median follow-up period was 3years. Lower-extremity disease was present in 85% (n = 310) of the patients. The best response for ILI/ILP as any line of therapy was 54% complete response (CR), 29 % partial response (PR), 8.2% stable disease (SD), and 9.1% progressive disease (PD). The CR/PR/SD/PD rates for first- versus second-line therapy were respectively 55%/29%/7.5%/8.2% versus 41%/26%/15%/18% (P = 0.09). As first-line therapy, ILI/ILP was associated with a significantly higher overall response rate (ORR) of 84% versus 68% (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.2-6.9; P = 0.02). The comparison showed no statistical difference in median in-field progression-free survival (PFS) (10.8 vs. 8.1months; P = 0.2), out-of-field PFS (13.5 vs. 15.3months; P = 0.4), or overall survival (OS) (4.1 vs. 4.5years; P = 0.7). For patients with unresectable melanoma ITM, ILI/ILP either as first- or second-line therapy provides high overallresponse rates. Although first-line therapy had a higher ORR, this did not translate to a difference in in-field PFS, indicating that ILI/ILP is indeed an effective salvage therapy also as second-line therapy.

Efficacy and safety analysis of China's first 10% IVIg (RonsenGlob) therapy in treating adult ITP.

A prospective, single-arm, open-label Phase III clinical trial was conducted across multiple centers in China from April 27, 2020, to June 15, 2021, to assess the efficacy and safety of 10% intravenous immunoglobulin (IVIg) in treating adult immune thrombocytopenic purpura (ITP). Within 7days of treatment initiation, the 10% IVIg group exhibited an overall response rate of 87.0%, with 32 patients (46.4%) achieving complete response and 28 patients (40.6%) demonstrating partial response, comparable to the 5% IVIg group. Notably, the median time to achieve a platelet count (PLT) of 50 × 109/L was significantly shorter for the 10% IVIg group at 2days (IQR: 2-3) versus 3days (IQR: 3-5) for the 5% IVIg group. Additionally, the 10% IVIg group reached a PLT of 100 × 109/L in 3days (IQR: 3-4), compared to 5days (IQR: 4-6) for the 5% IVIg group. Post-treatment bleeding scores significantly decreased, and no significant adverse reactions were reported. This inaugural study highlights the efficacy and safety of 10% IVIg in the urgent management of adult ITP, positioning it as a rapid therapeutic option.

Tumoricidal dosing approach with parenchymal sparing using voxel-based dosimetry in 90Y glass microspheres treatment of hepatocellular carcinoma.

We aimed to evaluate the effect of tumor absorbed doses (TAD) on treatment response in patients with hepatocellular cancer (HCC) treated with 90Y glass microspheres. We aimed to define a cutoff value for complete response (CR). The voxel-based dosimetry for the treatment of 66 HCC lesions in 56 patients was analyzed retrospectively. Nineteen patients had BCLC A, 23 patients had BCLC B, and 14 patients had BCLC C disease. Treatments were grouped as selective (radiation segmentectomy and super-selective segmentectomy, n:49) and nonselective (palliative treatments for tumors occupying >2 segments, n:17). Treatment response was evaluated by mRECIST criteria, defined as CR, partial response (PR), stable lesion (SL), and progressive lesion (PL). TAD associated with CR was analyzed. TAD was 525 ± 222 Gy in our cohort. Fifteen lesions had CR, 28 had PR, eight remained stable, and 15 lesions progressed. CR, PR, SL, and PL rates for selective vs. nonselective treatments were 31, 42, 12, and 14% vs. 0, 41, 11, and 47% for nonselective treatments, respectively (P:0.01). TAD was significantly associated with treatment response. Receiver operating characteristic analysis showed TAD > 475 Gy predicted CR with 100% sensitivity and 68% specificity (area under the curve = 0.83, P < 0.001). Overall survival declined as treatment response deteriorated. None of the patients had radiation-induced liver dysfunction on follow-up (6-21 months). Higher TAD is crucial for CR. Segmentectomy with TAD > 475 Gy is associated with favorable response and better survival in HCC patients. Even for palliative treatments, as high as reasonably tolerated doses must be applied to achieve a favorable response.

Pembrolizumab plus Lenvatinib in patients with metastatic Renal Cell Carcinoma: real-world evidences from the international ARON- 1 study

BackgroundPembrolizumab plus lenvatinib is a treatment option for metastatic Renal Cell Carcinoma (mRCC). In the ARON-1 study we investigated we the real-world experiences gained from the use of this combination for mRCC.MethodsWe retrospectively investigated real-world clinical outcomes of mRCC patients receiving pembrolizumab plus lenvatinib within the ARON-1 study. Overall survival (OS) was calculated from the start of pembrolizumab plus lenvatinib to death for any cause. Progression-Free Survival (PFS) was defined as the time from the start of pembrolizumab to progression or death from any cause. Duration of response (DoR) was defined as the time from the start of pembrolizumab to disease progression or death, whichever occurred first, in patients who achieved complete remission (CR) or partial response (PR). Overall Response Rate (ORR) was defined as the proportion of patients who achieve a CR or PR per RECIST criteria. Adverse events were retrospectively collected from electronic and paper charts and categorized by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.ResultsOverall, we included 202 mRCC patients treated with pembrolizumab plus lenvatinib. The median follow-up time was 15.1 months. The median OS was not reached (NR), with a median PFS of 25.6 months and an Overall Response Rate (ORR) of 59%. The median Duration of Response (DoR) was 26.2 months. G3-G4 adverse events (AEs) were observed in 92 patients (46%), with hypertension being the most common AE (13%).ConclusionsPembrolizumab plus lenvatinib is an effective and tolerable treatment for mRCC also in the real-world setting.

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.

Immunotherapy combined with chemotherapy: a promising therapeutic approach in the management of colonic squamous cell carcinoma—a case report

Colorectal squamous cell carcinoma (CSCC) is an exceedingly rare malignancy, accounting for approximately 0.41% of all colorectal cancers. This case report describes a 52-year-old male with a history of chronic bronchitis, varicose vein of the lower limb, diabetes, and Hepatitis B cirrhosis, who presented with worsening abdominal pain. The patient underwent a right hemicolectomy, and postoperative pathology revealed a moderately differentiated CSCC with proficient mismatch repair (pMMR) status. The patient was initially treated with the CAPEOX adjuvant chemotherapy regimen, the patient’s condition unfortunately progressed. Therefore, the treatment plan has been adjusted to include nab-paclitaxel and carboplatin, in combination with camrelizumab, an Anti-PD-1 therapy, for antitumor therapy. The combination therapy resulted in a partial response. This case highlights the potential efficacy of Anti-PD-1 therapy combined with chemotherapy in CSCC, suggesting a possible treatment approach for this rare cancer subtype.

Treatment of Intermediate-Risk Hepatoblastoma Using a Combined Cisplatin and Doxorubicin (PLADO) Regimen and Optimized Surgical Resection.

Complete resection of the primary tumor is critical for the survival of children with hepatoblastomas (HBs). This prospective clinical study aimed to clarify the outcome of a chemotherapy regimen comprising cisplatin and doxorubicin (PLADO) followed by definitive surgery conducted at the appropriate time in patients with intermediate-risk HB. Intermediate-risk HB was defined as patients without evidence of metastatic disease who met any of the following criteria: age ≥3years; PRETEXT IV disease; presence of more than one PRETEXT annotation factor. The study protocol consisted of four preoperative and two postoperative courses of PLADO. The appropriate surgeries were conducted at optimized timings via real-time central surgical reviews. The 3-year progression-free and overall survivals of the 33 intermediate-risk patients included were 78.7% and 87.9%, respectively. Preoperative PLADO resulted in a partial response in 83.9% of the patients. Microscopic complete resection was ultimately obtained in 31 (94%) patients. No patient required more than six preoperative courses before surgery or liver transplantation (LTx). Two patients never had surgery due to tumor progression. The outcome for patients with intermediate-risk HB was satisfactory. PLADO, combined with surgery (including LTx) conducted at the optimal time, appeared to cure most patients in this study.

Phase 1 study of talquetamab, a humanized GPRC5D x CD3 bispecific antibody, in Japanese patients with relapsed/refractory MM.

The bispecific antibody talquetamab demonstrated substantial responses in heavily pretreated relapsed or refractory multiple myeloma (RRMM) in the global phase 1/2 MonumenTAL-1 study. This study, evaluated the safety and efficacy of talquetamab in Japanese patients with RRMM pretreated with a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody. The primary endpoints were frequency and type of treatment-emergent adverse events (TEAEs) and serious AEs including dose-limiting toxicity (DLT). The secondary endpoints were overall response (ORR; partial response or better), duration of, and time to response. At data cutoff, 15 patients had received subcutaneous talquetamab at three doses (Cohort 1: 135 µg/kg weekly [QW, n = 4]; Cohort 2: 400 µg/kg [QW, n = 5]; Cohort 3: 800 µg/kg [Q2W, n = 6]). No DLTs, deaths, or AE-related dose reductions/treatment discontinuation were observed. Common TEAEs were neutropenia (60.0%), lymphopenia (53.3%), and CRS (46.7%). TEAEs of clinical interest (all Grade ≤ 2) were dysgeusia, skin toxicity, nail disorder, and dry mouth. With an overall median follow-up of 9.0 months, the ORR was 60.0% (95% confidence interval 32.3%, 83.7%). Talquetamab showed substantial responses in Japanese patients with RRMM, consistent with the global MonumenTAL-1 study, supporting its potential as a new standard of care for Japanese RRMM patients.

Efficacy of toripalimab in combination with anlotinib in recurrent undifferentiated pleomorphic sarcoma of the sinonasal region: a case report with biomarker analysis

BackgroundSoft tissue sarcoma (STS) typically originates in the muscles and is associated with a poor prognosis. Undifferentiated pleomorphic sarcoma (UPS) is the most commonly diagnosed subtype of STS; however, UPS occurring in the sinonasal region is exceedingly rare and lacks effective treatment options.ObjectiveThis case report presents a patient with sinonasal UPS who experienced disease progression after surgery and chemotherapy but showed a positive response to combination therapy with toripalimab and anlotinib. Additionally, it explores the underlying biomarkers associated with this case.CaseA 63-year-old woman with no significant past medical history was diagnosed with sinonasal UPS. The lesions recurred despite seven extensive surgical resections, and standard chemotherapy failed to control the disease, leading to progressive disease (PD).ResultsThe patient was treated with a combination of toripalimab and anlotinib, resulting in a significant partial response (PR) after just two cycles. Continued PR was observed after an additional six cycles, indicating the potential for a prolonged response with ongoing therapy. Genotyping and immunohistochemistry revealed that the sarcoma cells were rapidly dividing and enriched in vasculature prior to systemic treatment.ConclusionThese findings suggest that the combination of toripalimab and anlotinib may be an effective treatment option for advanced cases of UPS in the sinonasal region.

Ribociblib in Sequential Combination with Doxorubicin in Anthracycline-Naive Advanced Soft Tissue Sarcomas: Results of a Dose-Finding Phase 1B Study.

Doxorubicin is first-line treatment for metastatic soft tissue sarcomas (STS). Ribociclib, a CDK 4/6 inhibitor, targets the retinoblastoma pathway to induce cell cycle arrest at the G1/S cell cycle checkpoint. We hypothesized that administering ribociclib prior to doxorubicin to synchronize cell cycle progression among tumor cells may enhance the efficacy of doxorubicin. Doxorubicin-naive patients with metastatic STS were enrolled in this phase 1b study. Every 21d, subjects received ribociclib daily for 7d followed by 3d of no treatment before administration of doxorubicin. The primary objective was to establish the recommended phase 2 dose (RP2D) of the sequenced drug combination. Secondary objectives included progression-free survival and objective response rate (ORR). Exploratory correlative studies assessed pharmacokinetic (PK) and pharmacodynamic measures. Of 38 screened patients, 16 were enrolled and 15 were evaluable for dose determination. The most common reason for exclusion was lack of normal retinoblastoma protein (pRb) expression. At dose level 0 (ribociclib 400 mg, doxorubicin 75 mg/m2), 4 of 7 patients experience febrile neutropenia as a dose limiting toxicity (DLT). Of the 8 patients treated at dose level -1 (ribociclib 400 mg, doxorubicin 60 mg/m2), 1 had a DLT of grade 4 anemia. Three patients achieved partial response (ORR 20.0%). Ribociclib PK levels were lower than predicted. Phospho-pRb levels in on-treatment tumor biopsy tissue were variable and did not correlate with ribociclib plasma levels. The RP2D is ribociclib 400 mg followed by doxorubicin 60 mg/m2, which demonstrated an acceptable toxicity profile.

Case Report: Ensartinib as a first-line treatment for SMARCA4-deficient and EML4-ALK non-small cell lung cancer

SMARC4 is the catalytic subunit of the SWI/SNF chromatin remodeling complex and is one of the most common altered chromatin remodeling ATPases in cancer. Studies have indicated that SMARCA4 loss is associated with highly aggressive tumors, independently predicting shorter overall and disease-specific survival. SMARCA4-deficient non-small cell lung cancer (NSCLC) primarily affects male individuals, especially smokers, and is characterized by large, aggressive tumors. Cases of SMARCA4 deletion combined with actionable driver gene mutations (e.g., ALK) are rarely reported. In this report, we describe a male non-smoker diagnosed with SMARCA4-deficient, EML4-ALK non-small cell lung cancer who has been undergoing ensartinib targeted therapy for 3 months, resulting in a significant partial response. We also propose that, from a signaling perspective, the presence of SMARCA4 deficiency may influence the sensitivity of EML4-ALK NSCLC to targeted therapy, highlighting the need for further investigation into the underlying mechanisms and the exploration of novel therapeutic approaches.

Combined stereotactic radiation therapy and immunotherapy for metastatic uveal melanoma

AimUveal melanoma (UM) is a rare primary intraocular malignant tumor with an extremely poor prognosis. Our study evaluated the feasibility to improve metastatic UM treatment outcomes with a combined approach of immunotherapy and radiation therapy.MethodsThe retrospective study enrolled 24 patients with metastatic uveal melanoma who had combined treatment with stereotactic radiation therapy (RT) and immune checkpoint inhibitor therapy. 35% of patients received combination immunotherapy, and the others received mono-immunotherapy with anti-PD-1 drugs. All patients underwent stereotactic RT for metastases in the liver (75% patients), bones (8%), soft tissues (8%), brain (4%), and lungs (4%).ResultsOverall response rate (ORR) was 39.1%. Complete response (CR) was achieved in 8.7% patients and partial response (PR) – in 30.4% patients, median progression free survival (PFS) was 11.6 months [95% confidence interval (CI), 5.4-14.4], and median overall survival (OS) was 27.6 months [95% CI, 16.9 - 49.1].ConclusionsThe study has demonstrated a safe combination of stereotactic radiation therapy and immune checkpoint inhibitor immunotherapy in patients with metastatic uveal melanoma. The combination shows a potential treatment option for this patient cohort since no other effective therapies are available at present.

A multicenter, prospective, observational study of nivolumab readministration for advanced gastric cancer (NIVO RETURNS).

Combination treatment with an anti-programmed cell death-1 (PD-1) antibody, an immune checkpoint inhibitor (ICI), and chemotherapy is the standard treatment for patients with HER2-negative advanced gastric/esophagogastric cancer (AGC). ICI re-administration has been reported to have a clinical benefit for patients with lung cancer or melanoma. However, data on patients with AGC have not yet been collected. We plan to conduct a prospective, multicenter, observational NIVO RETURNS study to evaluate the efficacy and safety of nivolumab monotherapy re-administration in patients with AGC refractory to initial anti-PD-1 or anti-programmed cell death ligand-1 (PD-L1) antibody treatment. Patients who have achieved clinical benefits (complete response, partial response, or stable disease for ≥ 6 months) from prior treatment, including anti-PD-1/PD-L1 therapy, will be included. The primary endpoint will be the objective response rate to nivolumab re-administration. We anticipate that our findings will contribute to the improvement of survival outcomes as later-line treatment for AGC.Clinical trial registration: UMIN000050515, UMIN000051044.

Efficacy and safety of telitacicept in patients with class III-V lupus nephritis: A real-world retrospective cohort study.

Efficacy and safety of telitacicept in patients with class III-V lupus nephritis: A real-world retrospective cohort study.