Systemic Antitumor Therapy Research Articles

Characteristics of the tumor microenvironment and therapeutic progress in malignant pleural effusion

Malignant pleural effusion (MPE) can be secondary to various advanced malignant tumors. Although systemic anti tumor therapy may be effective in primary tumors, it cannot reduce the accumulation of MPE in proportion of the patients. The interaction of tumor cells, immune cells, and mesenchymal cells, as well as the abnormal proliferation of tumor-associated blood vessels, together create an immunosuppressive microenvironment for MPE, which promotes the abnormal proliferation of tumor cells and the accumulation of MPE. With the in-depth study of the tumor microenvironment, the application of local systemic anti-tumor therapy with local intrathoracic application of immune checkpoint inhibitors, immune cells, cytokines, and gene-mediated cytotoxic immunotherapy are able to alleviate the immunosuppressive tumor microenvironment and inhibit the accumulation of MPE. This article aimed to describe the tumor microenvironment in MPE and provide clues for identifying novel therapeutic targets.

A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer

Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor. This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813). Patients with locally advanced/metastatic HER2-positive gastric/gastroesophageal junction cancer and no prior systemic antitumor therapy were randomized 1:1:1 to 25mg/kg HLX22 (a novel anti-HER2 antibody)+ HLX02 (trastuzumab biosimilar)+ oxaliplatin and capecitabine (XELOX) (group A), 15mg/kg HLX22+ HLX02+ XELOX (group B), or placebo+ HLX02+ XELOX (group C) in 3-week cycles. Primary endpoints were progression-free survival (PFS) and objective response rate (ORR) assessed by independent radiological review committee (IRRC). Between November 29, 2021, and June 6, 2022, 82 patients were screened; 53 were randomized to group A (n= 18), B (n= 17), and C (n= 18). With 14.3months of median follow-up, IRRC-assessed median PFS was prolonged with the addition of HLX22 (A vs. C, 15.1 vs. 8.2months, hazard ratio [HR] 0.5 [95% confidence interval (CI) 0.17-1.27]; B vs. C, not reached vs. 8.2months, HR 0.1 [95% CI 0.04-0.52]). Confirmed ORR was comparable among groups (A vs. B vs. C, 77.8% vs. 82.4% vs. 88.9%). Treatment-related adverse events (TRAEs) were observed in 18 (100%), 16 (94.1%), and 17 (94.4%) patients, respectively. One (5.6%) patient in group C reported a grade 5 TRAE. Adding HLX22 to HLX02 and XELOX prolonged PFS and enhanced antitumor response in the first-line treatment of HER2-positive gastric cancer, with manageable safety. Shanghai Henlius Biotech, Inc.

Prognostic analysis of systemic antitumor therapy in young patients with advanced liver cancer: A cohort study.

Advanced liver cancer is the most common malignant tumor in the elderly, but it also occurs in young people in areas where hepatitis B virus is prevalent. The aim of the present study was to assess the efficacy of systemic antitumor therapy in young patients with advanced liver cancer and investigate the influencing factors. The baseline demographic and clinical data of 38 young patients (≤35 years old) with liver cancer were collected as group A and that of 79 elderly patients (≥55 years old) with liver cancer were collected as group B. There were no significant between-group differences regarding the proportion of patients with increased serum aspartate aminotransferase, low serum albumin, increased α-fetoprotein (AFP) and high Child-Pugh score. The median (m)PFS time in groups A and B was 3.9 and 8.3 months, respectively [hazard ratio (HR), 1.702; P=0.009]. The mOS in group A (17.6 months) was 12.4 months shorter than that in group B (HR, 1.799; P=0.010). In the subgroup analysis, male sex [HR, 1.73; 95% confidence interval (CI), 1.07-2.79], pathological diagnosis (HR, 1.79; 95% CI, 1.10-2.91), previous surgical treatment (HR, 2.16; 95% CI, 1.18-3.95), no tumor thrombus (HR, 2.45; 95% CI, 1.22-4.93), increased alanine aminotransferase (HR, 2.23; 95% CI, 1.07-4.65), increased aspartate aminotransferase (HR, 3.22; 95% CI, 1.62-6.39), normal total bilirubin (HR, 1.77; 95% CI, 1.09-2.87) and increased AFP (HR, 2.02; 95% CI, 1.19-3.41) were associated with shorter survival time in group A compared with those in group B (P<0.05). Group A also had a higher incidence of hyper-progressive disease (HPD) (31.6 vs. 3.8%; P<0.001). HPD was a risk factor for advanced liver cancer (HR, 4.530; 95% CI, 2.251-9.115; P<0.001]. In conclusion, the efficacy of systemic antitumor therapy in young patients was poorer compared with that in elderly patients. Young patients with liver cancer had a high HBV infection rate and were prone to HPD.

Synthetic genomic nanomedicine with triple-responsiveness for systemic anti-tumor therapy

To overcome the biological barriers in the journey of systemic gene delivery, a multifaceted genomic synthetic nanomedicine was elaborated and strategically equipped with a multiple of intriguing responsiveness. Particularly, core–shell plasmid DNA condensates were created based on polyionic complexation with block copolymer of polyethylene glycol (PEG)-polylysine (PLys), namely, the nanoscaled PLys&pDNA nanoparticle tethered with the biocompatible PEG surroundings. Furthermore, redox-reversible disulfide crosslinking was introduced into PLys&pDNA nanoparticle to accomplish adequate structural stabilities, and thermal-responsive polypropylacrylamide (PNIPAM) was introduced as the secondary intermediate surroundings onto the pre-formulated PLys&pDNA nanoparticle with the aim of preventing the potential enzymatic degradation from the environmental nucleases. Hence, hundreds of times prolonged survival and retention was determined in pertinent to the blood circulation properties. Additionally, the installation of a guide ligand at the distal end of PEG segments was proposed to encourage selective tumor uptake. A linear peptide of GPLGVRG, which is selectively susceptible to digestion by the tumor-enriched matrix metalloproteinase 2 (MMP-2), was used as the linkage between the shell and core. This peptide has been shown to detach the bio-inert PEGylation, resulting in further facilitated cell endocytosis and intracellular trafficking activities. Hence, the precisely defined synthetic nanomedicine, which exhibits desirable characteristics, efficient expression of the therapeutic gene in the affected cells, and contributed to potent therapeutic efficacy in systemic treatment of intractable tumors by encapsulating the anti-angiogenic gene.

A phase II study of tunlametinib in combination with vemurafenib in patients with BRAF V600-mutant advanced melanoma.

e21519 Background: The new MEK inhibitor tunlametinib combined with the BRAF inhibitor vemurafenib showed promising clinical activity in patients (pts) with BRAF V600-mutant solid tumors in a previous Phase I study (NCT03976050). Based on the result, we designed a phase IIa study to evaluate the efficacy and safety of tunlametinib plus vemurafenib in Chinese pts with BRAF V600 mutant melanoma. Methods: This open-label, single arm, multiple-center phase IIa study enrolled Chinese pts with BRAF V600E-mutant advanced melanoma, without restriction on the disease subtype (e.g., acral, mucosal, or cutaneous melanoma). Prior treatment was permitted, excluding BRAF/MEK inhibitors. Pts received oral tunlametinib at a dose of 9 mg twice daily and vemurafenib 720 mg twice daily. The primary endpoint was the objective response rate (ORR) per RECIST v1.1. Results: Between October 15, 2021, and June 22nd, 2022, 17 pts were enrolled and included in the analysis. Thirteen (76.5%) pts had received previous systemic antitumor therapy, with 12 (70.6%) receiving immunotherapy. Seven (41.2%) pts had acral melanoma, 8 (47.1%) pts had skin melanoma (non-acral) and 2 (11.8%) pts had mucosal melanoma. All pts had metastatic disease. With a median follow-up of 15.3 months (95%CI: 6.8; NE), 12 (70.6%) pts achieved confirmed partial response (PR), resulting in a confirmed ORR of 70.6% (95% CI: 44.0%-89.7%). The disease control rate was 100% (95% CI: 80.5%, 100.0%). The median progression-free survival (PFS) was 10.0 months (95% CI: 5. 5, NE). the duration of response (DOR) was 20.1 (95% CI: 4.2, NE). The overall survival (OS) was 21.6 months (95% CI: 14.5, NE), with a 12-months OS rate of 87.4% (95% CI: 58.1%, 96.7%). Subgroup analysis revealed that in pre-treated pts, the confirmed ORR was 76.9% (95% CI: 46.2%, 95.0%), the median PFS was 10.0 months (95% CI: 5.5, NE), while in previous untreated pts, the mPFS was 14.0 months (95% CI: 9.9, NE). In pts with skin melanoma, the confirmed ORR was 87.5% (47.3%, 99.7%), the mPFS was 10.0 months (95% CI: 5.5, NE), the mOS was 21.6 months (95% CI: 5.7, NE). In pts with acral melanoma, the ORR was 57.1% (95% CI: 18.4%,90.1%), the mPFS was 18.1 months (95% CI: 2.8, NE), the mOS not reached (12.3, NE). The most common adverse events included rash, pyrexia, and elevated blood creatin phosphokinase, most of which were of grade 1-2 severity. Grade 3 or higher TRAEs occurred in 12 (70.6%) pts, of which 41.2% were rash. Most AEs were manageable with supportive therapy or dose interruption. No treatment-related deaths were reported. Conclusions: The addition of a MEK inhibitor tunlametinib to vemurafenibexhibited promising clinical efficacy in Chinese patients with BRAF V600-mutant advanced melanoma, with a manageable safety profile. Additionally, notable effects were observed in pts with acral melanoma. The efficacy in pre-treated patients was comparable to that of similar agents in previous untreated patients. Clinical trial information: NCT05263453 .

A phase II study of cadonilimab plus mFOLFIRINOX as induction therapy for locally advanced pancreatic adenocarcinoma (LAPC).

TPS4213 Background: Locally advanced pancreatic adenocarcinoma (LAPC) constitutes a significant proportion of pancreatic cancer, which ranks among the most lethal malignancies globally. Treatment options specifically tailored for LAPC patients (pts) are scarce, and chemotherapy alone yields limited efficacy. Various studies have provided supportive evidence for the synergistic effects of combining immunotherapy with chemotherapy in the context of pancreatic cancer. Cadonilimab, a novel recombinant humanized bispecific antibody, holds the capability to concurrently inhibit PD-1 and CTLA-4 pathways, thereby restoring T-cell immune response to the tumor. This study aims to assess the efficacy and safety of combining cadonilimab with modified FOLFIRINOX for the treatment of LAPC. Methods: This ongoing phase II trial is enrolling pts with histologically or cytologically confirmed unresectable LAPC who have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 and have not previously received systemic anti-tumor therapy. Eligible pts will be administered cadonilimab (6mg/kg, intravenous drip, Day 1, every 2 weeks) plus mFOLFIRINOX (oxaliplatin 85mg/m2, Day 2 + leucovorin 400mg/ m2, Day 2 + irinotecan 150mg/ m2, Day 2 + 5-fluorouracil 2,400mg/ m2, continuous infusion for 46 hours) for a total of 4 cycles (8 weeks). After the completion of every 4 treatment cycles, pts will undergo imaging examinations of tumor lesions. Pts will receive treatment continuously until surgical resection, disease progression, intolerable toxic reactions, initiation of new anticancer drug treatments, withdrawal from the study, death, or loss of follow-up. Following the 12th cycle of treatment, maintenance treatment will consist of capecitabine or S-1 in combination with cadonilimab. The primary endpoint of this study was the R0/R1 resection rate. The main secondary endpoints include the objective response rate (ORR) per RECIST 1.1, progression-free survival (PFS), overall survival (OS), and safety assessments. Additionally, pts will undergo peripheral blood next-generation sequencing (NGS) panel analysis before and after treatment to investigate the correlation between circulating tumor DNA (ctDNA) changes, surgical decisions, and prognosis. Enrollment is ongoing. Clinical trial information: NCT06153368 .

Tifcemalimab combined with toripalimab and chemotherapy as 1st line treatment for extensive-stage small cell lung cancer (ES-SCLC): A phase Ib/II, open-label study.

8089 Background: Tifcemalimab, a humanized IgG4 monoclonal antibody against B and T lymphocyte attenuator (BTLA), has shown preliminary anti-tumor activities in combination with toripalimab (anti-PD-1) as a later line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). We further conducted a multi-cohort phase Ib/II study (NCT05664971) to evaluate the safety and efficacy of tifcemalimab combined with toripalimab and chemotherapy as a 1st line treatment for patients with advanced lung cancer. Here, we report the preliminary results from the ES-SCLC cohort. Methods: Patients without previous systemic anti-tumor therapy for ES-SCLC were eligible. Patients received tifcemalimab 200mg in combination with toripalimab 240mg and standard chemotherapy (etoposide + carboplatin/cisplatin) intravenously once every three weeks (Q3W) for 4 cycles, then followed by tifcemalimab plus toripalimab maintenance therapy until disease progression, intolerable toxicity, or completion of 2 years treatment. Primary endpoints included safety and objective response rate (ORR) by investigators per RECIST v1.1. Results: From 7/12/2023 to 12/6/2023, a total of 44 ES-SCLC patients were enrolled. As of Dec 28, 2023, the median follow-up duration was 8.3 weeks. The median age of the patients was 65.5 (range 48-73) years, and 84.1% (37/44) were males. Forty-one (93.2%) patients experienced treatment-emergent adverse events (TEAEs), and 26 (59.1%) experienced ≥ grade 3 TEAEs. The most common TEAEs included leukopenia (65.9%), neutropenia (63.6%), anemia (40.9%) and thrombocytopenia (40.9%). No treatment-related adverse events led to discontinuation of tifcemalimab and toripalimab. Four (9.1%) patients experienced immune related AE (irAEs), and 1 experienced ≥ grade 3 irAE. Among 37 evaluable patients, 32 PR and 5 SD were observed. The ORR was 86.5% (32/37) and the DCR was 100% (37/37). By the data cut-off date, 94.6% of the responses were ongoing and the median duration of response was not reached. The preliminary biomarker analysis of tumor tissue suggested 100% ORR was observed among patients with either PD-L1 or HVEM positive expression. Further biomarker analysis will be updated. Conclusions: Tifcemalimab in combination with toripalimab and chemotherapy showed a promising objective response rate with a manageable safety profile as a 1st line treatment for patients with ES-SCLC. Continued follow-up is ongoing for additional safety and efficacy (PFS and OS) evaluation after extended exposure. Clinical trial information: NCT05664971 .

Effect of antitumor therapy on microflora and oral mucosa in patients with malignant neoplasms

The present article investigates the relationship between the microbiota of the oral cavity and oral mucositis induced by systemic antitumor therapy in patients with malignant neoplasms. This article highlights modern ideas about the composition of the normal microbiota of the oral cavity and its changes during chemotherapeutic treatment.&#x0D; It has been shown that the normal oral microbiota includes representatives of such genera as Actinomyces, Corynebacterium, Fusobacterium, Leptotrichia, Neisseria, Prevotella, Streptococcus, and Veillonella. Moreover, it is emphasized that despite the existence of modern molecular genetic techniques and development of an oral microbiota database, determining the role of individual taxonomic units in oral homeostasis remains challenging.&#x0D; Existing studies of changes in the qualitative and quantitative composition of oral microflora against the background of drug antitumor therapy have demonstrated that treatment is associated with significant changes in the microbiological landscape of the oral cavity. An increase was noted in the number of Gram-negative anaerobic opportunistic flora and a decrease in the representation of protective commensal flora. It has been demonstrated that the components of a bacterial cell can modulate the local reactions of a macroorganism through a system of Toll-like receptors while acting in different directions.&#x0D; Several unresolved fundamental issues related to the role of oral microbiota in the pathogenesis of oral mucositis are highlighted.

Venous thrombosis during systemic antitumor therapy: risks, prognosis, treatment. A review

Venous thrombosis during systemic antitumor therapy: risks, prognosis, treatment. A review

HLX22 plus HLX02 and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer: A randomized, double-blind, multicenter phase 2 study.

354 Background: Gastric/gastroesophageal junction (G/GEJ) cancer represents a global healthcare challenge. With more than 1 million new cases estimated in 2020, it ranked fifth among all cancers. HER2 amplification or overexpression were reported in around 20% of advanced G/GEJ cancer cases. Despite the improved overall survival with trastuzumab plus chemotherapy, the prognosis remains unsatisfactory, and thus more effective treatments are needed. This study aimed to evaluate the combination of HLX22 (a novel anti-HER2 monoclonal antibody), HLX02 (a trastuzumab biosimilar), and chemotherapy for patients with G/GEJ cancer in the first-line setting. Methods: The study was unblinded 3 months after the last patient was enrolled. Patients with locally advanced or metastatic HER2-positive G/GEJ cancer and had not received prior systemic antitumor therapy were enrolled. The study consisted of 2 parts; current report will focus on part 1. In part 1, patients were randomized 1:1:1 to receive HLX22 25 mg/kg + HLX02 + XELOX (group A), HLX22 15 mg/kg + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles. Primary endpoints were PFS and ORR assessed by IRRC per RECIST v1.1. Secondary endpoints included other efficacy measures and safety. Results: As of July 30, 2023 (data cutoff), 53 patients were randomized to group A (n=18), B (n=17), and C (n=18), and were followed up for a median of 14.3 months. 44 (83.0%) patients were male. Main efficacy results are presented in Table. Tumor assessments reported in Table were performed by IRRC. Treatment-related adverse events (TRAEs) occurred in 18 (100.0%), 16 (94.1%), and 17 (94.4%) patients in the respective groups. Serious TRAEs were observed in 5 (27.8%) patients in group A, 1 (5.9%) in group B, and 1 (5.6%) in group C. Only 1 (5.6%) patient in group C had a grade 5 TRAE. Conclusions: Adding HLX22 to HLX02 + XELOX improved survival and antitumor response in patients with HER2-positive G/GEJ cancer in the first-line setting, with a manageable safety profile. Clinical trial information: NCT04908813 . [Table: see text]

Cytoreductive nephrectomy and its effect on prognosis in patients with disseminated renal cell carcinoma receiving treatment in wide clinical practice

Aim. To evaluate the effect of cytoreductive nephrectomy (CN) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) and to identify a group of patients who are candidates for cytoreductive surgical treatment.Materials and methods. We retrospectively analyzed a database of 403 patients with mRCC treated at the Moscow City Oncological Hospital No. 62 and the City Clinical Oncological Dispensary (Saint Petersburg) between 2006 and 2022. In total, 330 (81.9 %) patients underwent CN. All patients received systemic anti-tumor therapy: targeted anti-angiogenic therapy - 317 (78.6 %), cytokines - 61 (15.1 %), checkpoint inhibitors - 25 (6.2 %). The groups of operated and non-operated patients were unbalanced: CN was more often not performed in patients with multiple metastases, bone and liver lesions, laboratory abnormalities (anemia, increased serum alkaline phosphatase and lactate dehydrogenase) and unfavorable prognosis per IMDC (International mRCC Database Consortium) classification (p &gt;0.05 for all). Results. CN was associated with a significant increase in OS compared with primary tumor preservation in situ: median OS was 36 months with 95 % confidence interval 29.1-37.1, and 11 months with 95 % confidence interval 8.1-21.3, respectively (p &lt;0.0001). The benefit for OS in the CN group was also observed in clear-cell mRCC (p &lt;0.0001), grade G3 (p &lt;0.0001), multiple metastases (p &lt;0.0001) groups, and in the IMDC poor prognosis group (p &lt;0.0001). Conclusion. CN in selected mRCC patients results in a significant increase in OS. Further research is needed to determine selection criteria for surgical treatment candidates.

Clinical efficacy analysis of percutaneous “tripod” combined with radiofrequency ablation and bone cement filling in the treatment of periacetabular metastases

BackgroundTo investigate the clinical efficacy of a percutaneous “tripod” combined with radiofrequency ablation and bone cement filling surgery in treating acetabular bone metastases.MethodsWe retrospectively analyzed 11 patients who underwent percutaneous “tripod” combined with radiofrequency ablation and bone cement filling for acetabular bone metastases at a tertiary care hospital from February 2021 to December 2022.Results11 cases with 13 hips underwent this procedure, including two female patients who underwent both sides, and the rest were unilateral. All cases were followed up for 3–24 months, with a mean of 12 months and a median follow-up time of 11 months. Two of the 11 patients died by the final follow-up, and nine survived. One died 7 months after surgery, and one died 8 months after surgery; the survival of the deceased patients was 7.5 months (range: 7–8 months), with a median survival time of 7.5 months. All 11 patients completed the surgery successfully, and the average unilateral operation time was 167.4 min (148–193). The amelioration of postoperative pain, concomitant with improved quality of life, was observed significantly, ultimately resulting in a prolonged and sustained effect.ConclusionsThe combination of percutaneous “tripod”, radiofrequency ablation, and bone cement filling can effectively relieve pain without delaying the patient's systemic anti-tumor therapy and is a minimally invasive, safe, and effective procedure for the treatment of periacetabular metastases.

Impact of the STK11/KRAS co-mutation on the response to immunotherapy in a real-world pan-cancer cohort.

Immune checkpoint inhibitors are highly effective in treating various cancers. We analyzed the significance of the KRAS/STK11 co-mutation in relation to the efficacy of immune checkpoint inhibitors in pan-cancer patient cohort. We analyzed data from open-access research: MSK-IMPACT (molecular profiling data from patients receiving systemic antitumor therapy) and MSK-TMB (molecular profiling data from patients receiving immune checkpoint inhibitors). In both studies, high throughput sequencing was used for molecular profiling. A total of 10,336 patients receiving antitumor therapy (MSK-IMPACT study) and 1661 patients receiving immune checkpoint inhibitors (MSK-TMB study) were included in the analysis. Co-mutation STK11/KRAS was found in 156 (1.5%) and 46 (2.8%) patients in the two studies, respectively. Most patients with the STK11/KRAS co-mutation had non-small cell lung cancer (83% and 85% in the two studies, respectively). Among non-small cell lung cancer patients, the STK11 mutation was associated with a worse outcome for patients receiving systemic antitumor therapy, but not immune checkpoint inhibition therapy (HR for OS 1.90 [95% CI 1.36-2.65] and 1.44 [95% CI 0.88-2.37]). Co-mutation STK11/KRAS was also not associated with patient outcome in any of the studies (HR for OS 0.93 [95% CI 0.56-1.52] and 1.09 [95% CI 0.54-2.19]). High tumor mutational burden was associated with better outcome in the cohort of patients receiving immune checkpoint inhibitors. An analogous analysis among patients in the pan-cancer cohort (excluding patients with non-small cell lung cancer) showed STK11 mutations and high tumor mutational burden have a predictive role for the efficacy of immune checkpoint inhibitors, but not STK11/KRAS co-mutation. Co-mutation STK11/KRAS is common among patients with non-small cell lung cancer and is not an independent predictive marker for the efficacy of immune checkpoint inhibitors. Further studies are required to clarify the role of STK11 mutations in immune checkpoint inhibitor treatment response.

A decision tree model to predict liver cirrhosis in hepatocellular carcinoma patients: a retrospective study.

The severity of liver cirrhosis in hepatocellular carcinoma (HCC) patients is essential for determining the scope of surgical resection. It also affects the long-term efficacy of systemic anti-tumor therapy and transcatheter arterial chemoembolization (TACE). Non-invasive tools, including aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4), and γ-glutamyl transferase to platelet ratio (GPR), are less accurate in predicting cirrhosis in HCC patients. We aimed to build a novel decision tree model to improve diagnostic accuracy of liver cirrhosis. The Mann-Whitney U test, χ2 test, and multivariate logistic regression analysis were used to identify independent cirrhosis predictors. A decision tree model was developed using machine learning algorithms in a training cohort of 141 HCC patients. Internal validation was conducted in 99 HCC patients. The diagnostic accuracy and calibration of the established model were evaluated using receiver operating characteristic (ROC) and calibration curves, respectively. Sex and platelet count were identified as independent cirrhosis predictors. A decision tree model integrating imaging-reported cirrhosis, APRI, FIB-4, and GPR was established. The novel model had an excellent diagnostic performance in the training and validation cohorts, with area under the curve (AUC) values of 0.853 and 0.817, respectively. Calibration curves and the Hosmer-Lemeshow test showed good calibration of the novel model. The decision curve analysis (DCA) indicated that the decision tree model could provide a larger net benefit to predict liver cirrhosis. Our developed decision tree model could successfully predict liver cirrhosis in HCC patients, which may be helpful in clinical decision-making.

Functional tumor cell-intrinsic STING, not host STING, drives local and systemic antitumor immunity and therapy efficacy following cryoablation

BackgroundDespite its potential utility in delivering direct tumor killing and in situ whole-cell tumor vaccination, tumor cryoablation produces highly variable and unpredictable clinical response, limiting its clinical utility. The mechanism(s)...

Possibilities of remedial treatment of dermatological adverse events associated with cancer treatment using physical factors

Due to the improvement of oncologic services, optimization of surgical treatment methods, and the emergence of new approaches to systemic anti-tumor therapy, a gradual decrease in the mortality rate from malignant tumors has been observed. The changing clinical spectrum of side effects that develop during the treatment of malignant tumors determines the need to optimize approaches to remedial therapy. One of the most common side effects of drug and radiation anti-tumor therapy are dermatological adverse events. The use of physical factors is a promising area in supportive oncology, including with regard to dermatological side effects. This article presents a review of scientific publications devoted to the prevention and remedial treatment of dermatological side effects of anti-tumor therapy with the use of physical factors. The high safety profile of a number of techniques and their pronounced positive therapeutic effect, allowing for the continuation of life-saving drug and/or radiation therapy, are demonstrated. Optimization of approaches to accompanying physiotherapeutic treatment of dermatological adverse events and more active introduction into practical medicine of those methods of treatment that have already proven their effectiveness and safety are an essential scientific and practical task of modern medicine.

A phase 2 study of HLX07 as monotherapy or combination therapy in patients with locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma.

4029 Background: Esophageal cancer is one of the most common cancers worldwide with esophageal squamous cell carcinoma (ESCC) being the predominant histological subtype. Most patients are diagnosed at the advanced stage, and the prognosis remains poor. About 40–84% of ESCC cases showed overexpression of EGFR which was related to shorter overall survival and disease-free survival, indicating that treatment targeting EGFR could be a new strategy. This study aimed to evaluate the efficacy and safety of HLX07, a novel recombinant humanized anti-EGFR monoclonal antibody (mAb), as monotherapy or combination therapy in patients with locally advanced, unresectable/metastatic ESCC. Methods: In this open-label, multicenter phase 2 study, patients aged 18–75 years with histologically or cytologically confirmed locally advanced, unresectable/metastatic ESCC or esophageal adenosquamous carcinoma were enrolled. Patients with no prior systemic antitumor therapy were assigned to group A and given HLX07 1000 mg plus serplulimab 200 mg (anti-PD-1 mAb) and chemotherapy (5-FU 2400 mg/m2 + cisplatin 50 mg/m2), Q2W IV. Patients who had failed first-line immuno-chemotherapy combination or at least two lines of other systemic antitumor therapy were assigned to group B and given HLX07 monotherapy (1000 mg Q2W IV). The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) assessed by an independent radiological review committee and investigators per RECIST v1.1. Secondary endpoints included other efficacy measures, safety, pharmacokinetics, immunogenicity, and biomarker explorations. Results: As of February 4, 2023, 49 patients were enrolled in group A (n=30) and group B (n=19), with a median age of 64.5 and 59.0 years, respectively. 26 (86.7%) patients in group A and all patients in group B were male. The median follow-up duration was 2.9 months, and the preliminary efficacy was presented. Among the 42 efficacy evaluable patients (29 in group A and 13 in group B), investigator-assessed ORRs were 55.2% (95% CI 35.7–73.6%) and 23.1% (95% CI 5.0–53.8%) in the respective groups. Investigator-assessed median PFSs were not reached in group A and 1.5 months (95% CI 1.2–not evaluable) in group B. 15 (50.0%) patients in group A and 5 (26.3%) in group B had grade ≥3 treatment-emergent adverse events (AEs). AEs of special interest were observed in 16 (53.3%) and 11 (57.9%) patients, respectively, most commonly rash (43.3% vs 47.4%) and hypomagnesemia (33.3% vs 36.8%). No drug-related death was reported. Conclusions: The encouraging antitumor activity and manageable safety profile support further development of HLX07 as a new treatment option for patients with advanced ESCC, both in first-line and late-line settings. Clinical trial information: NCT05221658 .

A multicenter, single-arm, phase 2 study of surufatinib plus toripalimab for patients with advanced endometrial cancer.

5609 Background: Several immunotherapy monotherapies, or combined with antiangiogenic inhibitors, have shown antitumor efficacy in endometrial cancer (EMC) and been approved by FDA. However, therapeutic options for EMC after failure of first-line treatment remain scarce in China. The open-label, multi-cohort, single-arm phase 2 study was performed to evaluate the efficacy and safety of the combination of surufatinib (a small-molecule inhibitor of VEGFR 1-3, FGFR1 and CSF-1R) with toripalimab (an anti-PD-1 antibody) for Chinese patients (pts) with EMC after failure of one or more prior lines of systemic treatment. Methods: Pts with EMC who progressed or were intolerable after at least one prior line of systemic antitumor therapy were eligible and enrolled. They received 21-day cycles of surufatinib 250 mg orally, QD, plus toripalimab 240 mg IV, Q3W, until disease progression or reaching the maximum treatment duration with toripalimab of 24 months, or other protocol-specified criteria. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: From August 2020 to March 2022, 28 pts were enrolled and received the combination treatment (median duration: 4.6 months). Median age was 58 years (range: 50-71), and 22 (78.6%) pts were endometrioid adenocarcinoma at diagnosis. 9 (32.1%) pts had received ≥2 prior lines of therapy. As of 28 Dec 2022, the median follow-up duration was 16.8 months. Microsatellite status was available in 25 pts. 20 with mismatch repair-proficient (pMMR) and 5 with mismatch repair-deficient (dMMR) were determined. All 28 pts were evaluable with at least one post-baseline tumor assessment. Efficacy results were: confirmed ORR, 28.6% (8 partial response [PRs]); DCR, 82.1%; mDoR, 5.7 months; mPFS (95%CI), 5.4 months (2.7, 8.3); 12-month OS rate, 71.0%. Among pts with pMMR, the confirmed ORR was 25.0%; DCR was 85.0%; mDoR was 4.2 months; mPFS (95%CI) was 4.0 months (2.7, 8.3); 12-month OS rate was 75.4%. All pts experienced at least one treatment-emergent adverse event (TEAE), and 19 (67.9%) of them reported grade ≥3 TEAEs. The most common (≥5% pts) grade ≥3 TEAEs were hypertension (28.6%), aspartate aminotransferase increased (14.3%), alanine aminotransferase increased (10.7%), proteinuria (7.1%), Gamma-glutamyltransferase increased (7.1%) and malignant neoplasm progression (7.1%). No new safety signals were observed. Conclusions: Surufatinib plus toripalimab had a promising antitumor activity and a manageable safety profile in pts with EMC after failure of one or more prior lines of systemic therapy. Clinical trial information: NCT04169672 .

Updated results of first-line serplulimab versus placebo plus chemotherapy in PD-L1–positive esophageal squamous cell carcinoma: A randomized, double-blind, multicenter phase 3 study (ASTRUM-007).

e16016 Background: Immune checkpoint inhibitors plus chemotherapy (chemo) improve antitumor efficacy as first-line treatment in patients with esophageal squamous cell carcinoma (ESCC). However, the optimal target population for this combination therapy remains uncertain. At ESMO Asia Congress 2022, we presented results from the interim analysis of the phase 3 study of serplulimab (anti-PD-1 antibody) plus chemo as first-line treatment for PD-L1–positive (CPS ≥1) ESCC patients. Here we report the results from an updated analysis, which is also the final analysis of overall survival (OS). Methods: In this randomized, double-blind, multicenter phase 3 study, patients with histologically confirmed locally advanced or distantly metastatic, PD-L1–positive ESCC who had no prior systemic antitumor therapy were randomized 2:1 to receive serplulimab 3 mg/kg or placebo plus chemo (5-FU + cisplatin) intravenously Q2W. Randomization was stratified by PD-L1 expression level (CPS ≥10 vs CPS &lt; 10), age (≥65 vs &lt; 65 years), and disease status (locally advanced vs distantly metastatic). The primary endpoints were IRRC-assessed progression-free survival (PFS) per RECIST v1.1 and OS. Secondary endpoints included other efficacy measures, safety, quality of life, and biomarkers. Results: Between June 19, 2019 and December 17, 2021, 976 patients were screened and 551 were randomized (serplulimab-chemo, n = 368; placebo-chemo, n = 183). At this updated analysis, median follow-up duration was 24.2 months. Median OS was significantly longer in the serplulimab-chemo group than the placebo-chemo group (14.6 vs 11.2 months; hazard ratio [HR] 0.70, 95% CI 0.57–0.86; P = 0.0006). IRRC-assessed median PFS per RECIST v1.1 was prolonged with the addition of serplulimab (6.5 vs 5.3 months; HR 0.58, 95% CI 0.47–0.72). Efficacy improvements were also observed in confirmed objective response rate (58.7% vs 42.1%) and duration of response (median, 7.1 vs 4.6 months) as assessed by IRRC per RECIST v1.1. Grade ≥3 treatment-related adverse events were reported in 203 (53.1%) and 82 (48.8%) patients in the respective groups. Incidence of grade ≥3 immune-related adverse events was higher in the serplulimab-chemo group compared to the placebo-chemo group (9.2% vs 3.0%). Fifteen deaths (3.1% in the serplulimab-chemo group and 1.8% in the placebo-chemo group) that might be related to study treatment were reported. Conclusions: With another 9.3 months of follow-up, the encouraging efficacy and manageable safety of serplulimab plus chemo as first-line treatment in patients with PD-L1–positive advanced ESCC were maintained, further supporting the development of serplulimab plus 5-FU and cisplatin for previously untreated ESCC patients. Clinical trial information: NCT03958890 .

Chemotherapy combined with anlotinib, toripalimab and stereotactic radiotherapy in oligo-metastatic nasopharyngeal carcinoma: A prospective, multicenter phase II clinical study.

e18011 Background: Distant metastasis is the main cause of nasopharyngeal carcinoma (NPC) related death while there are few treatment options for it. How to further improve the survival of NPC patients with distant metastases is an urgent problem to be solved in clinical practice. This study investigated the efficacy and safety of chemotherapy in combination with anlotinib (a multi-target tyrosine kinase inhibitor), toripalimab, and stereotactic radiotherapy(SBRT) in treatment of metastatic NPC. Methods: This is a prospective, multi-centered, single-arm, phase II trial (ChiECRCT20210147). Patients with histologically confirmed non-keratinous carcinoma and post-treatment metastatic NPC (stage IVb, AJCC 8th) who had no local recurrence and received no systemic antitumor therapy for metastatic lesions previously were enrolled. No more than 5 metastatic lesions (metastatic sites include lung, liver, bone, etc.), and with at least one measurable target lesion according to RECIST1.1. Other inclusion criteria included 18-65 years old and ECOG 0-1. All patients received gemcitabine (1000 mg/m2, ivgtt, d1/8), cisplatin (80 mg/m2, ivgtt, d1), toripalimab (240mg, ivgtt, d1) and anlotinib (12mg, oral, qd, d1-14) every 3 weeks for 6 cycles, then followed by toripalimab (240mg, ivgtt, d1) and anlotinib (12mg, oral, qd, d1-14) every 3 weeks for 11 cycles. The SBRT was initiated after 2 cycles of chemotherapy (bone GTV 30-45Gy/3-5f, liver and lung GTV 45-60Gy/4-6f). The primary endpoint was objective response rate (ORR). Here we report the results of a preliminary analysis. Results: Between January 2022 and January 2023, a total of 19 patients were enrolled (13 males and 6 females), the median age was 46 years old. At the data cutoff date on January 31, 2023, 15 patients were eligible for the evaluation of tumor response with metastatic lesions. 100% of the patients (15 of 15) had a response and the confirmed ORR was 100% (complete response, n = 4; partial response, n = 11) for metastatic lesions. The most common treatment-related adverse events (TRAE) of any grade were leukopenia (15 of 15,100%), anaemia(13 of 15, 93.3%), decreased appetite (10 of 15, 66.7%), hypothyroidism (6 of 15, 40.0%), rash(5 of 15, 33.3%) and pneumonitis (5 of 15, 33.3%). Grade 3-4 TRAE included leukopenia (3 of 15, 20.0%) and no fatal adverse events occurred. Conclusions: This preliminary analysis indicated that chemotherapy combined with anlotinib, toripalimab, and stereotactic radiotherapy had promising efficacy and favorable tolerance as treatment of oligo-metastatic NPC. Clinical trial information: ChiECRCT20210147 .