Improved Disease Control Rate Research Articles

Clinical Efficacy and Safety of transarterial chemoembolization Combined with Targeted Therapy for primary hepatocellular carcinoma.

To explore the clinical efficacy and safety of transarterial chemoembolization (TACE) combined with targeted therapy for primary hepatocellular carcinoma (PHC). This was a retrospective study. Retrospective selection of 150 PHC patients admitted to the Renmin Hospital, Hubei University of Medicine January 2019 and June 2021 were included. The patients were divided into the control group and the experimental group according to their treatment regimens. The control group received TACE treatment, while the experimental group received TACE combined with targeted therapy. We analyze the relevant data of two groups of patients and evaluate the clinical efficacy and safety of TACE combined with targeted therapy. The tumor remission rate and control rate in the control group were 41.89% and 75.68%, respectively, while those in the experimental group were 77.63% and 90.79%, with statistically significant differences (p<0.05). The 1-year and 3-year recurrence rates in the control group were 52.71% and 98.65%, respectively, while those in the experimental group were 39.47% and 61.84%, with statistically significant differences (p<0.05). After treatment, the AFP, VEGF, ALT, and AST in the experimental group were significantly reduced compared to the control group (p<0.05). During the treatment period, the incidence and severity of nausea, vomiting, and fever in the experimental group were significantly lower than those in the control group (p<0.05). The clinical efficacy of TACE combined with targeted therapy for PHC is superior to that of TACE alone, with improved disease control rate, improved long-term survival rate, and good safety.

Efficacy comparison of fruquintinib, regorafenib monotherapy or plus programmed death-1 inhibitors for microsatellite stable metastatic colorectal cancer.

Regorafenib (R) and fruquintinib (F) are the standard third-line regimens for colorectal cancer (CRC) according to the National Comprehensive Cancer Network guidelines, but both have limited efficacy. Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair (MSS/pMMR) CRC. Due to the lack of studies comparing the efficacy between F, R, F plus programmed death-1 (PD-1) inhibitor, and R plus PD-1 inhibitors (RP), it is still unclear whether the combination therapy is more effective than monotherapy. To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC (mCRC) patients in clinical practice. A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital, and 313 MSS/pMMR mCRC patients were finally included. A total of 313 eligible patients were divided into F (n = 70), R (n = 67), F plus PD-1 inhibitor (FP) (n = 95) and RP (n = 81) groups. The key clinical characteristics were well balanced among the groups. The median progression-free survival (PFS) of the F, R, FP, and RP groups was 3.5 months, 3.6 months, 4.9 months, and 3.0 months, respectively. The median overall survival (OS) was 14.6 months, 15.7 months, 16.7 months, and 14.1 months. The FP regimen had an improved disease control rate (DCR) (P = 0.044) and 6-month PFS (P = 0.014) and exhibited a better trend in PFS (P = 0.057) compared with F, and it was also significantly better in PFS than RP (P = 0.030). RP did not confer a significant survival benefit; instead, the R group had a trend toward greater benefit with OS (P = 0.080) compared with RP. No significant differences were observed between the R and F groups in PFS or OS (P > 0.05). FP is superior to F in achieving 6-month PFS and DCR, while RP is not better than R. FP has an improved PFS and 6-month PFS compared with RP, but F and R had similar clinical efficacy. Therefore, FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.

Final outcomes analysis of the cell product SQZ-PBMC-HPV Phase 1 trial in incurable HPV16+ solid tumors shows improved overall survival in patients with increased CD8+ T cell tumor infiltration.

Cancer vaccines strive to induce robust, antigen-targeted, T-cell-mediated immune responses but have struggled to produce meaningful regression in solid tumors. An autologous cell vaccine, SQZ-PBMC-HPV, was developed by SQZ Biotechnologies using microfluidic squeezing technology to load PBMCs with HPV16 E6 and E7 antigens in HLA-A*02+ patients. The SQZ-PBMC-HPV-101 Phase 1 trial (NCT04084951) enrolled patients with incurable HPV16+ cancers. Here, we present a post hoc analysis of the relationship between Posttreatment CD8+ T cell infiltration and patient outcomes. SQZ-PBMC-HPV was administered as monotherapy every 3 weeks. Tumor samples were collected pre-dose and post-dose 4 weeks after treatment start. Biomarkers including CD8, MHC-I, E6, E7, GZMB, and Ki67 were evaluated by immunohistochemistry, immunofluorescence, and RNA in situ hybridization, and were correlated with clinical response, survival, and drug product composition. Eighteen patients had paired pre- and post-dose biopsies. Six (33%) had an increase in CD8+ T cell density in tumor parenchyma between screening and C2D8. Patients with increased CD8+ T cell density had improved disease control rate (66.7% vs 16.7%) and median overall survival (606.5 days vs 170.0 days, p = 0.0078). Drug product was significantly enriched for higher T cells and lower monocytes in the increased CD8+ T cell density group. In patients with incurable HPV16+ solid tumors treated with SQZ-PBMC-HPV, an increase in CD8+ T cell density within the tumor parenchyma was associated with superior disease control rate and overall survival. The product composition for patients with increased CD8+ T cell density was enriched for T cells.

Real-world effectiveness and safety of trifluridine-tipiracil (FTD/TPI) and bevacizumab (BEV) in refractory metastatic colorectal cancer (mCRC): The BeTAS trial.

51 Background: In the Sunlight Trial, the combination of FTD/TPI + BEV demonstrated significantly extended Overall Survival (OS) and Progression-Free Survival (PFS), along with an improved Disease Control Rate (DCR), compared to FTD/TPI alone in patients with refractory mCRC. The BeTAS trial aimed to evaluate the real-world effectiveness and safety of the FTD/TPI + BEV combination in patients with refractory mCRC. Methods: We conducted a multicenter, retrospective, observational study involving patients with mCRC who were refractory or intolerant to standard therapies (including oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF, and anti-EGFR if RAS/BRAF wild-type) and were treated with FTD/TPI + BEV at six university hospitals affiliated with the Galician Research Group on Digestive Tumors (GiTUD) in Northwest Spain. Results: A total of 110 patients were enrolled in the BeTAS trial between July 2019 and August 2023. The median age was 66 years (range 33-88 years), with 62.7% being male. Notably, 18.2% of patients had an ECOG performance status of 2, 50.9% had RAS mutations, 27.3% had three or more metastatic locations, and 72.7% had liver metastases. Additionally, 26.4% had a time since the diagnosis of the first metastases of less than 18 months, and 46.4% were categorized as the poor prognostic Tabernero´s Subgroup. Most patients (77.3%) received FTD/TPI + BEV as a third-line treatment, with 88.9% having received previous anti-VEGF therapy. Notably, 13.6% received FTD/TPI at a dose of 30 mg/m2, and 6.4% received prophylactic GCSF. The median number of cycles received was 4 (range 1-21 cycles). Among 97 evaluable patients, the overall response rate (ORR) was 2.1%, and the disease control rate (DCR) was 46.4%. With a median follow-up of 15.5 months, the median PFS was 4.2 months (95% CI, 3.5-4.9 months), and the median OS was 9.9 months (95% CI, 7.3 - 12.5 months). The most common grade 3-4 toxicities included neutropenia (41.8%), asthenia (7.3%), and hepatic toxicity (5.5%). No treatment-related deaths were reported. Conclusions: The BeTAS trial findings affirm the real-world effectiveness and safety of FTD/TPI + BEV in the context of routine clinical practice, even in a population with a poor prognosis and extensive prior treatment history.

Response of Locally Advanced Pancreatic Cancer to Intratumoral Injection of Large Surface Area Microparticle Paclitaxel: Initial Report of Safety and Clinical Outcome.

Large surface area microparticle paclitaxel (LSAM-PTX) provides an intratumoral (IT) chemotherapeutic depot. Safety, tolerability, and tumor response to IT LSAM-PTX delivered by endoscopic ultrasound-fine needle injection were evaluated in subjects with unresectable locally advanced pancreatic cancer (LAPC). Ten subjects treated in a dose escalation phase and 22 additional subjects receiving 2 injections, 4 weeks apart, of 15 mg/mL LSAM-PTX were followed for 12 months. Paclitaxel pharmacokinetics were evaluated, imaging at 3 and 6 months determined tumor response, and multiplex immunofluorescence was conducted to characterize local immune response. Most treatment-emergent adverse events were attributed to LAPC. Plasma paclitaxel levels were negligible. Eight subjects' tumors became resectable after IT LSAM-PTX, and 5 of 6 (83%) were resected with R0. Multiplex immunofluorescence of resected tumors demonstrated increased T cells, natural killer cells, and macrophages and decreased myeloid-derived suppressor cells. Six-month disease control rate was 94%, and median overall survival was 19.7 months in the 2-injection subjects. For nonresected and resected groups, overall survival times were 18.9 and 35.2 months, respectively. Neoadjuvant IT LSAM-PTX, in combination with SOC, was well tolerated and may provide benefits to LAPC patients, evidenced by enhanced immune response, improved disease control rate, restaging leading to surgery, and extended survival.

Multidisciplinary management of pediatric malignant rhabdoid tumor based on 5 years of experience at a tertiary care center

Malignant rhabdoid tumor (MRT) is a highly aggressive tumor that occurs mostly in young children with extremely poor prognosis. Standardized and effective treatment strategies for MRT have yet to be established because of its rarity. Here, we report our single-institutional experience involving MRT treatment. Patients with newly diagnosed MRT between March 2016 and October 2021 were included. The clinical characteristic, treatment-related toxicities, clinical outcomes, and prognostic factor were retrospectively analyzed. A total of 18 patients with MRT were enrolled during the 5years. The median age was 42.8months (range 10 to 82years). Among the 18 patients, 9 patients died after a median of follow-up 26months (range 3 to 42months). The 1-year event-free survival (EFS) and 3-year overall survival (OS) rates of the entire cohort were 63% (95% CI 46% to 74%) and 67% (95% CI 49% to 82%), respectively. Univariate analysis of patients who underwent gross or total resection followed by adjuvant chemotherapy and radiotherapy demonstrated an improvement in 1-year EFS. However, only gross resection and total resection predicted a better 3-year OS. Surgical excision is still the mainstream treatment for MRT. Postoperative adjuvant treatments including chemotherapy and radiotherapy contribute to improved disease control rate. Our single-institute experience may provide insights into the multimodal treatment of MRT.

Special issue "The advance of solid tumor research in China": FGFR4 alterations predict efficacy of immune checkpoint inhibitors in nonsmall cell lung cancer.

Immune checkpoint inhibitors (ICIs), which represent the new standard of care for advanced nonsmall cell lung cancer (NCSLC), are not effective in many patients. Biomarkers are needed to guide treatment. Sequencing data of an ICI-treated cohort were analyzed to identify genomic signatures predicting ICI efficacy, followed by validation using multiple independent cohorts. Their predictive mechanism was explored by evaluating the tumor immune microenvironment and tumor mutational burden (TMB). In the discovery cohort, patients carrying FGFR4 alterations (FGFR4altered ) had a better objective response rate (ORR) (50.0% vs 19.4%; P=.057) and improved median progression-free survival (mPFS) (13.17 vs 3.17 months; HR 0.37; 95% CI 0.14-1; P=.04) than wild-type patients (FGFR4wt ). In the publicly available validation cohorts, FGFR4 alterations correlated with higher ORR (100% vs 31%; P=.028), longer median overall survival (mOS) (not reached [NR] vs 11 months; HR 0.28, 95% CI 0.09-0.89, P=.02), and mPFS (NR vs 6.07 months; HR 0.05, 95% CI 0-3.94, P=.039). FGFR4 alterations were confirmed as an independent predictor of superior PFS (P=.014) and OS (P=.005). FGFR4altered patients also exhibited a significantly improved disease control rate (100% vs 60%, P=.045) and prolonged mPFS (9.70 vs 3.16 months; P=.095) compared to FGFR4wt patients in our Shanghai Pulmonary Hospital cohort. FGFR4 alterations associated with a higher TMB levels, more CD8+ T cells in the tumor stroma, and a higher M1/M2 ratio for tumor-associated macrophages in the tumor center and stroma. Thus, FGFR4 alterations may serve as a potential independent predictor of ICI efficacy in NSCLC.

Efficacy of anlotinib for advanced SCLC patients: A real-world study.

e20621 Background: Anlotinib is a novel small molecule multi-target tyrosine kinase inhibitor, which has been approved as a third-line therapy for patients with advanced small cell lung cancer (SCLC) by NMPA in Aug 2019. ALTER 1202 trial has demonstrated that anlotinib significantly prolonged progress-free survival (PFS) and improved disease control rate (DCR) of advanced SCLC patients. Since the efficacy of patients in real clinical practice is affected by many factors, the objective of this study was to assess the efficacy of anlotinib for patients with advanced SCLC in real world. Methods: This is a multi-center, non-interventional, prospective real-world study and all registered data are collected from real clinical practice cases. Patients diagnosed as advanced SCLC and treated with anlotinib were included. The primary endpoint was PFS, and secondary endpoints included overall survival (OS), objective response rate (ORR), DCR and safety. Results: Until Dec 2021, a total of 44 eligible patients were included, with a median age of 62 years, including 34 males (77.3%) and 10 females (22.7%). Among them, 38 patients (86.4%) were diagnosed as a limited stage SCLC and 6 patients (13.6%) diagnosed extensive stage. All patients have not received other targeted therapies before. The median PFS was 6.0 months (95%CI 2.4-5.8), and the median OS was 15.9 months (95%CI 9.1-18.83). At the data cut-off date, 1 patient was assessed as CR, 22 patients were assessed as PR, 15 patients were assessed as SD and 4 patients were assessed as PD. The ORR was 52.3% and the DCR was 86.4%. Conclusions: Significant improvement in OS and PFS were found for advanced SCLC patients in this real-world study. This exhibited that anlotinib has a potential efficacy over previous treatment models. Of course, safety must be further observed subsequently.

Neutrophil-to-Lymphocyte Ratio to Predict the Efficacy of Immune Checkpoint Inhibitor in Upper Gastrointestinal Cancer.

Although the effectiveness of immune checkpoint inhibitors (ICIs) in upper gastrointestinal (UGI) cancer including esophageal squamous cell carcinoma (ESCC) and gastric/gastroesophageal adenocarcinoma (GEA) has been proven, prediction of their efficacy remains unknown. This study aimed to develop optimal serum nutritional indicators or a combination of blood cell components to predict the efficacy of ICI before beginning UGI cancer treatment. We retrospectively reviewed the data of 61 UGI cancers (31 ESCC and 30 GEA) patients treated with nivolumab or pembrolizumab. We investigated the impact of serum albumin level, total lymphocyte count (TLC), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) on the efficacy of ICIs and long-term survival. The median cutoff value was adopted separately in ESCC and GEA. NLR-Low was significantly correlated with better overall survival (p=0.014), and PLR-Low was significantly correlated with improved disease control rate and better progression-free survival in UGI cancer patients. Both results indicate that a better prognosis is correlated to a greater number of lymphocytes. Multivariate analysis revealed that NLR-High [hazard ratio (HR)=2.865; 95% confidence interval (CI)=1.030-7.937; p=0.044] was the only independent poor prognostic factor. NLR-Low has the potential to predict the good efficacy of ICIs and survival outcomes in patients with UGI cancer. NLR could be useful in determining the optimal treatment strategies for these patients.

Transarterial Chemoembolization (TACE) Combined With Sorafenib versus TACE in Patients With BCLC Stage C Hepatocellular Carcinoma – A Retrospective Study

Advanced-stage hepatocellular carcinoma is a heterogeneous group with limited treatment options. TACE has been advocated recently by various study groups. The purpose of this study was to evaluate if TACE in combination with sorafenib, as well as TACE alone, was safe and efficacious in treating BCLC stage C HCC. A retrospective evaluation of the clinical data of 78 patients with BCLC stage C HCC who received either TACE-sorafenib (TS) combination therapy or TACE monotherapy as their first treatment was done. The two groups were compared in terms of radiological tumor response 1 month after the intervention. The two groups were also compared in terms of time to progression (TTP), overall survival (OS), and adverse events. The disease control rate (44.9% and 25.8%, respectively, P=0.09) was higher in the TScombination group than in the TACE monotherapy group after 1 month of treatment. The TS combination group had significantly superior TTPand OSthan the TACE group (TTP was 4.6 and 3.1 months, respectively, P=0.001), and OS was 10.1 and 7.8 months, respectively, P < 0.001). The TACE-S group had a greater cumulative survival time at 6 months, 9 months, and 1 year than the TACE group (97.9%, 51.1%, 25.7% vs. 90.4%, 51.6%, and 0%, respectively). TS combination therapy in advanced-stage (BCLC-C) HCC significantly improved disease control rate, TTP, and OS compared with TACE alone, without any significant increase in adverse reactions.

Molecular profiling of advanced malignancies guides first-line N-of-1 treatments in the I-PREDICT treatment-na\xefve study

BackgroundMalignancies are molecularly complex and become more resistant with each line of therapy. We hypothesized that offering matched, individualized combination therapies to patients with treatment-naïve, advanced cancers would be feasible and efficacious. Patients with newly diagnosed unresectable/metastatic, poor-prognosis cancers were enrolled in a cross-institutional prospective study.MethodsA total of 145 patients were included in the study. Genomic profiling (tissue and/or circulating tumor DNA) was performed in all patients, and PD-L1 immunohistochemistry, tumor mutational burden, and microsatellite status assessment were performed in a subset of patients. We evaluated safety and outcomes: disease-control rate (stable disease for ≥ 6 months or partial or complete response), progression-free survival (PFS), and overall survival (OS).ResultsSeventy-six of 145 patients (52%) were treated, most commonly for non-colorectal gastrointestinal cancers, carcinomas of unknown primary, and hepatobiliary malignancies (53% women; median age, 63 years). The median number of deleterious genomic alterations per patient was 5 (range, 0–15). Fifty-four treated patients (71%) received ≥ 1 molecularly matched therapy, demonstrating the feasibility of administering molecularly matched therapy. The Matching Score, which reflects the percentage of targeted alterations, correlated linearly with progression-free survival (R2 = 0.92; P = 0.01), and high (≥ 60%) Matching Score was an independent predictor of improved disease control rate [OR 3.31 (95% CI 1.01–10.83), P = 0.048], PFS [HR 0.55 (0.28–1.07), P = 0.08], and OS [HR 0.42 (0.21–0.85), P = 0.02]. Serious adverse event rates were similar in the unmatched and matched groups.ConclusionsPersonalized combination therapies targeting a majority of a patient’s molecular alterations have antitumor activity as first-line treatment. These findings underscore the feasibility and importance of using tailored N-of-1 combination therapies early in the course of lethal malignancies.Trial registrationI-PREDICT (NCT02534675) was registered on August 25, 2015.

Transarterial Chemoembolization Combined with Sorafenib in Patients with BCLC Stage C Hepatocellular Carcinoma.

PurposeTranscatheter arterial chemoembolization (TACE) and targeted therapy have become common methods in the treatment of advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the safety and efficacy of TACE combined with sorafenib (TACE-sorafenib) and TACE alone for the treatment of Barcelona clinical stage C HCC.MethodsThe clinical data of 75 patients with BCLC stage C HCC who received TACE-sorafenib or TACE as the initial treatment were retrospectively analyzed. Tumor response, time to progression (TTP), overall survival (OS), and adverse events were compared at 1 month after surgery in the two groups.ResultsOne month after treatment, the disease control rate in the TACE-sorafenib group was higher than that in the TACE group alone (82.76% and 57.50%, respectively, P = 0.018). The median values of TTP and OS in the TACE-sorafenib group were longer than those in the TACE group (TTP was 7.6 and 3.4 months, respectively, P = 0.002; OS was 13.6 and 6.3 months, respectively, P = 0.041). The cumulative survival time at 3 months, 6 months, and 1 year was higher in the TACE-sorafenib group than in the TACE group (83.5%, 71.2%, 45.7% vs 57.4%, 40.6%, 21.2%). Sorafenib-related side effects such as hypertension, hand-foot syndrome, and oral ulcers were more common than those in the TACE group alone (P<0.05).ConclusionCompared with TACE treatment alone, TACE combined with sorafenib in BCLC-C stage HCC significantly improved disease control rate, TTP, and OS, and no significant increase in adverse reactions was observed.

Trans-catheter arterial chemoembolization plus Sorafenib, an unsuccessful therapy in the treatment of hepatocellular carcinoma?: A systematic review and meta-analysis.

Background:Trans-catheter arterial chemoembolization (TACE) plus Sorafenib is recommended as one of the primary means for treating hepatocellular carcinoma (HCC). This updated meta-analysis focuses on identifying the efficacy and safety of TACE plus Sorafenib versus TACE, which remains controversial despite years of exploration.Method:PubMed, Medline, Embase, China Journal Full-text Database, Wanfang Database, and Weipu Database were used to retrieve the studies which are about comparing the clinical efficacy and safety of TACE+Sorafenib with TACE alone. The Review Manager (Version 5. 3) software was used to perform a meta-analysis of the results of studies which met the inclusion criteria recommended by the Cochrane Collaboration.Result:Compared with TACE for treating primary HCC, TACE combined with Sorafenib can improve the 1 year, 2 years, 3 years, and 5 years overall survival rate (OS) of patients, respectively, and also improve disease control rate (DCR) and objective response rate (ORR). In terms of adverse reactions, the treatment group can lead to more complications significantly, such as hand-foot skin reaction, hypertension, diarrhea, rash, hair loss, and so on, most of which are relevant to Sorafenib related adverse reactions, but most patients have a good prognosis after symptomatic treatment.Conclusion:The clinical efficacy of TACE combined with Sorafenib in treating primary hepatocellular carcinoma is better than TACE, and the safety is acceptable.

Analysis of cognition for regular laboratory monitoring of HBeAg negative with chronic HBV infection

Objective To investigate the cognition influencing factors of regular laboratory monitoring of HBeAg negative in chronic HBV infection, and analyze the related factors of HBeAg conversion. Methods From January 2015 to March 2017, a total of 302 chronic HBV infected patients in Jinin Infectious Disease Hospital were investigated with a questionnaire about disease related cognition.Single factor and multiple factors Logistic regression analysis was used to analyze the influencing factors of regular monitoring behavior and HBeAg conversion.At the same time, 163 cases of HBeAg negative HBV infection were divided into the two groups: regular and irregular monitoring, and disease related laboratory tests and the outcomes were analyzed. Results Psychological pressure(OR=4.339, 95%CI: 1.322-14.243), antiviral treatment(OR=5.149, 95%CI: 1.628-16.283), knowledge of hepatitis B(OR=3.306, 95%CI: 1.108-9.867) and the stability of disease(OR=3.229, 95%CI: 1.094-9.528) were the regular monitoring promoting factors(all P<0.05). Antiviral therapy(OR=0.298, 95%CI: 0.108-0.822), virus gene mutation(OR=0.202, 95%CI: 0.048-0.856), and duration of disease(OR=0.340, 95%CI: 0.122-0.949) were related factors of HBeAg conversion(all P<0.05). The serum levels of ALT, ALB, AFP and HBV-DNA in the HBeAg negative regular monitoring group were (68±34)IU/L, (40±12)g/L, (23.0±5.9)μg/L, (2.0±1.3)copies/mL, respectively, which in the non-regular monitoring group were (126±56)IU/L, (35±10)g/L, (78.0±12.8)μg/L, (3.9±1.7)copies/mL, respectively, the differences were statistically significant (t=2.323, 2.097, 2.109, 2.234, all P<0.05). Conclusion HBeAg negative patients is a key group to monitor and control disease progression.Regular laboratory monitoring is better.Medical staff should enhance patients' cognition education and improve disease control rate. Key words: Hepatitis B virus; Hepatitis B surface antigens; Biosurveillance; Cognition

Retrospective analysis of efficacy and safety of Gemcitabine-based chemotherapy in patients with metastatic pancreatic adenocarcinoma experiencing disease progression on FOLFIRINOX.

Metastatic pancreatic adenocarcinoma (MPA) represents a highly lethal condition. Despite the improvements seen with FOLFIRINOX, there is no randomized data to guide treatment selection beyond this regimen. We aimed to evaluate the outcomes of patients with MPA progressing on FOLFIRINOX who were treated with Gemcitabine-based chemotherapy afterwards. We included patients aged 18 years or older, treated for MPA with FOLFIRINOX in the first-line setting and who experienced disease progression, with Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and treated with at least one cycle of Gemcitabine-based chemotherapy in second or further lines of treatment. We used descriptive statistics to characterize the study population and Cox proportional-hazards models to describe factors associated with survival. As an exploratory analysis, we compared the outcomes of patients treated with single-agent Gemcitabine with those of patients undergoing Gemcitabine-based polychemotherapy. The study population consisted of 42 patients. Median age was 59 years and 78.6% of patients presented ECOG 0-1. Thirty-three patients (78.6%) were treated with Gemcitabine-based chemotherapy in the second-line setting and 27 patients (64.3%) were treated with single-agent Gemcitabine. Objective response rate and disease control rate were 2.4% and 33.4%, respectively. Median progression-free survival (PFS) and median overall survival (OS) were 2.9 and 5.5 months, respectively. Six-month PFS and OS rates were 19.2% and 46.2%, respectively. We observed no significant difference in OS according to the type of Gemcitabine-based chemotherapy, despite numerically improved disease control rate and PFS for those treated with Gemcitabine-based polychemotherapy. In multivariate analysis, ECOG 2 (vs. ECOG 0-1) was the only factor significantly associated with inferior PFS and OS. a subgroup of patients with MPA derives benefit from treatment with Gemcitabine-based regimens after FOLFIRINOX. There is a suggestion that Gemcitabine-based combinations, in particular Gemcitabine plus Nab-Paclitaxel, provide superior outcomes compared to single-agent Gemcitabine. Additionally, treatment in this setting should be offered carefully to patients with ECOG 2, as they present shorter survival and increased risk of toxicity.

FcγRIIA and IIIA polymorphisms predict clinical outcome of trastuzumab-treated metastatic gastric cancer.

Trastuzumab has substantial antitumor activity in metastatic gastric cancer. One such mechanism by which it exerts its antitumor activity is antibody-dependent cell-mediated cytotoxicity, which has been reported to be influenced by FcγRIIA and IIIA polymorphisms. This study is the first to assess their impact on trastuzumab efficacy in patients with metastatic gastric cancer. We retrospectively examined 42 Her-2-positive patients receiving fluorouracil and platinum-based chemotherapy and trastuzumab, and 68 Her-2-negative patients receiving fluorouracil and platinum-based chemotherapy only as the first-line treatment. FcγRIIA and IIIA polymorphisms were assessed, and their associations with efficacy in both settings were analyzed. In patients treated with trastuzumab, the FcγRIIA H/H genotype was associated with significantly superior progression-free survival (PFS) (hazard ratio [HR] [95% CI]: 0.36 [0.16–0.82], adjusted HR [95% CI]: 0.18 [0.07–0.48], P=0.001). When combining FcγRIIA and IIIA polymorphisms, the FcγRIIA H/H or FcγRIIIA V/V genotype was associated with a significantly improved disease control rate (P=0.04) and PFS (HR [95% CI]: 0.29 [0.13–0.67], adjusted HR [95% CI]: 0.17 [0.07–0.45], P<0.001). As expected, no association of FcγRIIA and IIIA polymorphisms with efficacy was found in patients receiving chemotherapy only. We concluded that FcγRIIA and IIIA polymorphisms might predict disease control rate and PFS in metastatic gastric cancer patients receiving trastuzumab treatment.

The Efficacy and Risk Profile of c-Met inhibitors in Non-small Cell Lung Cancer: a Meta-analysis.

c-MET inhibitors are considered as a kind of novel drugs in non-small cell lung cancer (NSCLC) treatment. However, the results of different clinical studies involving c-MET inhibitors were not consistent. In this report, we performed Meta-analysis to investigate the beneficial and harmful effects of these drugs from 9 studies including 1611 patients in target drug groups and 1605 patients in control groups. As a result, patients in target drugs group had longer progression free survival (PFS) (HR 0.80, 95% CI 0.66–0.99, p = 0.04) but not overall survival (OS) than those in control group, especially in Asian (HR 0.57, 95% CI 0.42–0.76, p < 0.001), Non-squamous (HR 0.79, 95% CI 0.64–0.97, p = 0.03), Phase III (HR 0.66, 95% CI 0.50–0.86, p = 0.002), previous treated (HR 0.77, 95% CI 0.63–0.95, p = 0.01) and small molecular compounds subgroups (HR 0.62, 95% CI 0.50–0.78, p < 0.001). In addition, target drugs did not affect the objective response rate (ORR) but improved disease control rate (DCR) (RR 1.22, 95% CI 1.02–1.46, p = 0.03) of NSCLC patients. Our study first indicated that targeting c-MET therapies improved PFS and DCR in advanced or metastatic NSCLC patients, especially in previous treated Asian patients with adenocarcinoma.

641P - FcγR IIA and IIIA polymorphisms predict clinical outcome of trastuzumab treated metastatic gastric cancer

Trastuzumab has substantial anti-tumor activity in metastatic gastric cancer, and one mechanism is antibody-dependent cell-mediated cytotoxicity (ADCC), which has been reported to be influenced by FcγR II A and III A polymorphisms. This retrospective study is the first to assess their impact on trastuzumab efficacy in patients with metastatic gastric cancer. We retrospectively included 42 Her-2 positive patients receiving fluorouracil and platinum based chemotherapy and trastuzumab, and 68 Her-2 negative patients receiving fluorouracil and platinum based chemotherapy only as first line treatment. FcγR II A and III A polymorphisms were assessed and their associations with efficacy in both settings were analyzed. In patients treated with trastuzumab, FcγR II A H/H genotype was associated with significantly superior progression-free survival (PFS) (hazard ratio (HR) and 95% confidence interval (CI): 0.36 (0.16-0.82), adjusted HR and 95% CI: 0.18 (0.07-0.48), P = 0.001). Combining FcγR II A and III A polymorphisms, FcγR II A H/H or FcγRIII A V/V genotype was associated with significantly improved disease control rate (DCR) (P = 0.04) and PFS (HR and 95% CI: 0.29 (0.13-0.67), adjusted HR and 95% CI: 0.17 (0.07-0.45), P < 0.001). As expected, no association of FcγR II A and III A polymorphisms with efficacy was identified in patients receiving chemotherapy only. FcγR II A and III A polymorphisms might predict DCR and PFS in metastatic gastric cancer receiving trastuzumab treatment.

SPACE – A randomized study of SBRT vs conventional fractionated radiotherapy in medically inoperable stage I NSCLC

BackgroundStereotactic body radiotherapy (SBRT) has been introduced for small lung tumors due to excellent local control and few side effects, even though there are no comparative studies. SPACE (Stereotactic Precision And Conventional radiotherapy Evaluation) is the first randomized phase II trial comparing SBRT and conventional fractionated radiotherapy (3DCRT). MethodsPatients with stage I medically inoperable NSCLC were randomized to receive SBRT to 66Gy in 3 fractions (one week) or 3DCRT to 70Gy (7weeks). Patients were followed to assess efficacy, toxicity and HRQL. FindingsBetween 2007 and 2011, 102 patients were randomized. Mean age 74 (57–86), 60% women, the vast majority (92%) had COPD or cardiovascular comorbidity. The SBRT arm included more patients with T2-tumors (p=0.02) and male gender (p=0.35). The median follow-up was 37months with a 1-, 2- and 3-year PFS of: SBRT: 76%, 53%, 42% and 3DCRT: 87%, 54% 42%, HR=0.85 (95% CI 0.52–1.36) with no difference between the groups and no difference in OS (HR=0.75, 95% CI 0.43–1.30). At the end of the study 70% of SBRT patients had not progressed compared to 59% (3DCRT, p=0.26). Toxicity was low with no grade 5 events. Pneumonitis of any grade was observed in 19% (SBRT) and 34% (3DCRT, p=0.26), and esophagitis in 8% and 30% respectively (p=0.006).HRQL was evaluated with the EORTC QLQ 30 and LC14 module and patients treated with 3DCRT experienced worse dyspnea (p=0.01), chest pain (p=0.02) and cough (>10 points difference). InterpretationThere was no difference in PFS and OS between SBRT and conventionally treated patients despite an imbalance of prognostic factors. We observed a tendency of an improved disease control rate in the SBRT group and they experienced better HRQL and less toxicity. SBRT is convenient for patients and should be considered standard treatment for patients with inoperable stage I NSCLC.

Anti-epidermal growth factor receptor-targeted therapy in upper gastrointestinal tract cancers: a meta-analysis

This meta-analysis evaluated the efficacy and safety of anti-epidermal growth factor receptor (EGFR) treatment of patients with upper gastrointestinal (GI) tract cancers. A systematic search of multiple databases identified seven randomized controlled trials. Anti-EGFR combination therapy improved disease control rate (DCR) in all patients and progression-free survival (PFS) in patients receiving the same dose of standard therapy as patients receiving standard therapy alone. Combinations of anti-EGFR with non-capecitabine chemotherapy further improved DCR, whereas combinations with capecitabine masked the benefits of DCR and worsened PFS. Overall survival was apparently lower in patients without metastasis, and PFS was apparently improved in patients with squamous cell carcinoma of the esophagus and esophagogastric junction. Anti-EGFR treatment was associated with higher rates of cardiac events, hand–foot syndrome, rash, hypomagnesemia, diarrhea and mucositis and lower rates of neutropenia. Combinations of anti-EGFR agents with non-capecitabine chemotherapy or better supportive care may benefit patients with upper GI tract cancers.