Clinical trials of targeted therapy (TT) and immunotherapy (IT) for highly aggressive advanced melanoma have shown marked improvements in response and survival rates. However, real-world data on treatment patterns and clinical outcomes for patients with advanced BRAF V600 mutant melanoma are ultimately scarce. The study was designed as an observational retrospective chart review study, which included 382 patients with advanced BRAF V600 mutant melanoma, who received TT in a real-world setting and were not involved in clinical trials. The data were collected from twelve medical centers in Russia. The objective response rates (ORRs) to combined BRAFi plus MEKi and to BRAFi mono-therapy were 57.4% and 39.8%, respectively. The median progression-free survival (PFS) and median overall survival (OS) were 9.2 months and 22.6 months, respectively, for the combined first-line therapy; 9.4 months and 16.1 months, respectively, for the combined second-line therapy; and 7.4 months and 17.1 months, respectively, for the combined third- or higher-line therapy. Analysis of treatment patterns demonstrated the effectiveness of the combined TT with BRAF plus MEK inhibitors in patients with brain metastases, rare types of BRAF mutations, and across lines of therapy, as well as a well-tolerated and manageable safety profile.
Analysis of long-term treatment results of 101 primary gastric cancer patients at various stages of the tumor process followed during 1 - 41 months (median - 6,4 months) from the onset of specific treatment are presented depending on the levels of soluble forms (s) of PD-1 receptor and its ligand PD-L1 in blood plasma. Overall survival assessed by Kaplan-Meyer analysis and with the help of Cox multiparametric regression model was applied as the criterion of prognostic value. It was found that at high (≥ 35 pg/ml) sPD-L1 levels in blood plasma, the overall survival of patients with gastric cancer was statistically significantly lower than at the marker’s levels below 35 pg / ml (p <0.045): 1-year survival comprised 78 and 96%, 2-year - 52 and 78%; 3-year - 40 and 61% at high and low sPD-L1 respectively. Median survival of patients with high plasma sPD-L1 comprised 29 months, of those with low sPD-L1 was not achieved during the whole follow-up period. This trend was observed not only in the total group of stage I-IV gastric cancer patients, but also in patients at the early stages of the disease, though sPD-L1 did not show an independent prognostic value in multiparametric model. At the same time, the overall survival of patients with gastric cancer did not depend on the baseline levels sPD-1 in blood plasma. Thus, soluble ligand sPD-L1 can be considered as a potentially valuable factor for prognosis of gastric cancer patients’ survival, and, probably, of anti-PD-1/PD-L1 treatment efficiency, but further studies and patients’ monitoring are required to prove this statement.
Results of comparative ELISA investigation of pretreatment sPD-1 and sPD-L1 content in blood plasma of 100 gastric cancer patients at various disease stages aged 25 to 81 years are presented. Control group included 60 practically healthy donors aged 18 - 68 years. Plasma sPD-L1 concentrations did not differ between gastric cancer patients and control group, and sPD-1 levels were statistically significantly lower in patients than in healthy donors (p<0.0001). Positive correlation (R=0.38; p=0.003) was revealed between plasma sPD-1 and sPD-L1 levels in control group and negative (R= -0.26; p=0,009) - in gastric cancer patients. ROC curve revealed the best sPD-1 cut-off level (< 21 pg/ml) with 77% sensitivity and 63.3% specificity, which is not sufficient for its application as diagnostic marker. Statistically significant increase of plasma sPD-L1 from stage I to stage IIIC (R=0.50; p=0.000011) was found. Analysis of associations between the evaluated markers’ levels and indices of gastric cancer expansion according to TNM system revealed statistically significant positive associations of plasma sPD-L1 levels with T (tumor invasion depth) and N (number of affected lymph nodes) indices: R=0.33; p=0.00093, and R=0.27; p=0.0099 respectively. sPD-L1 level was significantly increased in patients with low differentiated adenocarcinoma and cricoid-cell cancer as compared to highly differentiated adenocarcinoma (p=0.02 and p=0.004 respectively); in patients with cricoid-cell cancer it was also higher than in those with moderately differentiated adenocarcinoma (p=0.043) and undifferentiated cancer (p=0.049). Plasma sPD-1 level did not depend on disease stage, TNM system indices and tumor histological structure. Thus, soluble ligand sPD-L1, but not its receptor sPD-1, plasma level is increased in patients with unfavorable clinical and morphological characteristics, may be regarded as potentially valuable prognostic factor for gastric cancer patients’ survival, and probably as a predictor of anti - PD-1/PD-L1 treatment efficiency.
There is a continued unmet medical need in pts with relapsed/refractory Hodgkin's lymphoma (RR HL). Curing HL pts who have refractory disease after salvage chemotherapy, who relapse after ASCT, or those who are not candidates for ASCT, remains a clinical challenge due to limited effective treatments. There are data available indicating that brentuximab vedotin (BV) brings considerable promise for the treatment of pts with RR HL. Information about BV treatment effectiveness and tolerability both from physician's and patient's perspective is worthwhile in this difficult patient population. We aimed to evaluate clinical and patient-reported outcomes in RR HL patients receiving BV as >2nd treatment line. Here we report the outcomes with respect to clinical response, tolerability, quality of life (QoL) and symptoms after 3 mos of BV treatment. The total number of pts to be included in the multicenter observational real-world study is 70 pts with RR HL who received BV 1.8 mg/kg q3w till disease progression, intolerance toxicity of BV or refusal. Treatment response was assessed using RECIST criteria v. 1.0. Adverse events (AEs) were assessed in accordance with NCI CTCAE v. 4.03. For QoL assessment pts filled out RAND SF-36, for symptom assessment - ESAS questionnaire; also pts filled out PGIC scale for self-assessment of changes in their health. For QoL analysis paired t-test, Mann-Whitney test, Wilcoxon test and χ2 were used. The analysis was performed in the group of 55 pts RR HL (median age - 28 years, range 18-67, 54.5% males) who were involved in the study: 63.6% pts had advanced stage (III-IV) at diagnosis; ≥50% pts had B-symptoms (58.2%); 82% pts - ECOG 0-1. All the pts received a median of 3 previous treatment lines; among them 14 pts (25.5%) failed to ASCT in the past; half of pts were primary chemotherapy resistant (49%). Before BV treatment start QoL was dramatically worsened for all SF-36 scales (p<0.05). All the pts experienced symptoms, 83.3% pts had moderate-to-severe symptoms. The most frequent (>70% pts) symptoms were drowsiness, tiredness, anxiety, and worse wellbeing. More than half pts had moderate-to-severe drowsiness,tiredness, depression, lack of appetite and worsened wellbeing before BV treatment start. After 3 mos of BV treatment objective response was registered in 55% pts with 27.5% complete response. Adverse events of grade I-II were reported in 8 pts (20%) and were consistent with known toxicities. Most common adverse events (≥10%) were increasing ALT and AST (each 4/8), peripheral neuropathy, fatigue, skin itch (each 3/8). Severe adverse event (III grade) not related with BV occurred in one patient (2.5%) - sepsis, respiratory insufficiency due to agranulocytosis (BV was temporary stopped). During BV treatment meaningful QoL improvement was revealed for all SF-36 scales (p<0.05), excluding mental health. IQoLI significantly increased at 3 mos after treatment start as compared to baseline: 0.260 at baseline vs 0.390 at 3 mos (p<0.001). Proportion of pts with significant Integral QoL Index (IQoLI) impairment dramatically decreased during treatment as compared to baseline: 60% before treatment vs 35% at 3 mos (χ2, p=0.05). The most pronounced meaningful improvement was revealed for role functioning scales (∆>20.0). The severity of the vast majority of symptoms excluding depression significantly decreased during 3 mos of treatment (p<0.05). Total Symptom Score by ESAS significantly decreased at 3 mos after BV treatment start (35.8 vs 25.4, p=0.001). Also according to PGIC, 90% pts noted the improvement of their health. The first results obtained in this multicenter observational real world study demonstrate notable activity of BV as a treatment modality for RR HL. BV showed a safety profile consistent with known toxicities. BV treatment was accompanied with dramatic QoL improvement and significant decrease of symptom burden already after 3 mos of treatment. Evaluation of BV treatment outcomes both from physician's and patient's perspective may provide unique information which will be helpful in decision making for patients with RR HL. Disclosures Ionova: Takeda, BMS: Other: Principal Investigator of IISR, Research Funding. Baryakh:Takeda: Consultancy, Honoraria, Speakers Bureau.
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