LBA5504 Background: Prior results from ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945) showed that pembro + CCRT and then continued after CCRT provided statistically significant and clinically meaningful improvements in OS and PFS vs CCRT alone in pts with newly diagnosed, previously untreated, high-risk LACC. We present the final analysis (FA) results from this study. Methods: Eligible pts with newly diagnosed, previously untreated, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of lymph node status) were randomized 1:1 to 5 cycles of pembro 200 mg or placebo (pbo) Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. The CCRT regimen included 5 cycles (with optional 6th dose) of cisplatin 40 mg/m 2 Q1W + EBRT then brachytherapy. Pts were stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), stage at screening (stage IB2-IIB vs III-IVA) and planned total radiotherapy dose (<70 Gy vs ≥70 Gy equivalent dose). Primary endpoints are PFS per RECIST version 1.1 by investigator and OS. Results: 1060 pts were randomized to pembro + CCRT (n=529) or pbo + CCRT (n=531). At the protocol-specified FA (Jan 7, 2025, data cutoff), median follow-up was 41.9 mo (range, 24.8-55.0). 86 pts had received post-progression immunotherapy; of those, 64 had received pembro. Pembro + CCRT continued to show clinically meaningful improvements in OS and PFS vs pbo + CCRT (Table). The benefit of pembro + CCRT was generally consistent in prespecified subgroups, including pts with stage IB2-IIB node-positive disease (OS HR=0.92 [95% CI, 0.62-1.38]; PFS HR=0.84 [95% CI, 0.63-1.14]). The grade ≥3 TRAE incidence was 69.5% in the pembro + CCRT group and 61.5% in the pbo + CCRT group. Conclusion: With an additional 12 mo median follow-up, pembro + CCRT continued to show clinically meaningful improvements in OS and PFS vs pbo + CCRT in pts with high-risk LACC and had a manageable safety profile. These data are consistent with the prior interim analysis and provide further support for pembro + CCRT as the new standard of care for this population. Clinical trial information: NCT04221945 . Summary of PFS and OS in ENGOT-cx11/GOG-3047/KEYNOTE-A18. Final Analysis 07JAN25 Interim Analysis 2 08JAN24 Interim Analysis 1 09JAN23 Pembro + CCRT Pbo + CCRT Pembro + CCRT Pbo + CCRT Pembro + CCRT Pbo + CCRT OS, median (95% CI) NR (NR-NR) NR (NR-NR) NR (NR-NR) NR (NR-NR) NR (NR-NR) NR (NR-NR) 36-mo OS 81.8% 74.4% 82.6% 74.8% NR (NR-NR) NR (NR-NR) HR (95% CI) 0.73 (0.57-0.94) 0.67 (0.50-0.90); P =0.0040 0.73 (0.49-1.07); P =0.0541 PFS, median (95% CI) 47.6 (47.6-NR) 47.5 (41.0-NR) NR (NR-NR) NR (32.0-NR) NR (NR-NR) NR (NR-NR) 24-mo PFS 70.6% 59.7% 70.6% 58.6% 67.8% 57.3% HR (95% CI) 0.72 (0.59-0.87) 0.68 (0.56-0.84) 0.70 (0.55-0.89); P =0.0020 NR=not reached.
Lung cancer is one of the most significant health problems globally due to its high prevalence and mortality rates. Innovative treatment regimens are needed to improve survival rates and reduce mortality from this disease in clinical practice. Objective. To evaluate the effectiveness and safety of a combination therapy consisting of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) in the treatment of advanced non-small cell lung cancer (NSCLC). We also aim to identify the optimal patient population for whom this treatment regimen would be most beneficial in real-world clinical practice. Material and methods. A retrospective analysis of the medical records of 58 patients who received a combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) at medical institutions in the Chelyabinsk region between January 2020 and November 2023 was conducted. Results. The median age of the 58 participants was 62 years (range: 38—84). The median duration of ABCP treatment was 11.3 months. Disease control (partial response or stable disease) was achieved in 84.2% (48) of patients. The median progression-free survival was 15.1 months (95% confidence interval (CI): 11.7—20.3). The mPFS among patients with brain metastases was 24.8 months (95% CI: 19.2—40.7)), p=0.05, and the median overall survival has not been reached yet. Conclusion. The study demonstrated that ABCP therapy shows high antitumor efficacy in real-world clinical settings for patients with advanced NSCLC. The objective response rate and progression-free and overall survival were equivalent or superior to those observed in the IMpower150 study. A subgroup analysis showed that patients with brain metastases can benefit from this combination therapy. The safety profile of ABCP was characterized by an acceptable profile with a very low incidence of immune-mediated adverse events. The data obtained allow us to consider ABCP combination therapy an effective strategy for the treatment of advanced NSCLC.
Background. A Russian phase IV observational study was initiated to evaluate the efficacy and safety of lenvatinib with pembrolizumab (Len-Pembro) in patients with advanced renal cell carcinoma (RCC) receiving therapy in real-world practice. This article is based on the results of the third analysis conducted with a median follow-up of 23.1 months and reflects data on the efficacy and safety of Len-Pembro in Russian patients. Aim. To evaluate the real-world efficacy and safety of Len-Pembro in patients with advanced RCC with a median follow-up increased to 23.1 months. The primary outcome of the study was progression-free survival (PFS), the secondary outcomes included overall survival (OS), progression-free survival on next-line therapy (PFS2), objective response rate (ORR), duration of response, as well as safety. Materials and methods. The study included data from 165 patients with verified advanced RCC who received Len-Pembro at 36 centers in the Russian Federation from February 05, 2018 to July 30, 2025. The median age was 60 (20–76) years, and 70.3% of the participants were male. Most patients (74.6%) presented with Karnofsky performance score of ≥80%, metachronous metastases (50.9%) of clear cell RCC (93.3%) in 1 organ (75.2%), and had not received any anticancer treatment (91.0%). The IMDC favorable prognosis group included 40 (24.2%), intermediate – 92 (55.8%), and unfavorable prognosis – 33 (20.0%) patients. The median follow-up reached 23.1 (0.5–72.9) months. A total of 110 (66.7%) patients completed Len-Pembro therapy, and 51 (30.9%) patients received next-line treatment. Results. Median PFS reached 25.8 (95% confidence interval – CI 17.0–34.5) months, 23-month PFS – 52.6%; median OS was 39.9 (95% CI 26.9–52.8) months, 23-month OS – 73.1%; median PFS2 was 33.2 (95% CI 23.4–41.1) months, 23-month PFS2 – 66.9%. The ORR was 49.1%, including 3.0% of complete responses, and the disease control rate was 89.1%. The median duration of response reached 29.7 (95% CI 24.9–34.6) months. The incidence of any adverse events (AEs) was 78.8%, severe AEs occurred in 29.1%, fatal AES – in 1.2%, immune-related AEs – 17.0%, severe immune-related AEs – 6.7%. Conclusion. In real-world practice, with increased follow-up duration, the values of PFS, OS, and PFS2 were comparable to those obtained in the registrational study, with a lower ORR and a satisfactory safety profile of the combination of Len-Pembro in advanced RCC.
Introduction. Improvement of conservative therapy of polypous rhinosinusitis is important for scientific and practical otorhinolaryngology. Aim. To study the therapeutic possibilities of a recombinant antibody to immunoglobulin E for polypous rhinosinusitis in patients with bronchial asthma with insufficient efficacy of intranasal glucocorticosteroid therapy. Materials and methods. The study was performed with the participation of 78 patients out of 204 registered with pulmonologists and otorhinolaryngologists aged 18-45 years, with an average weight of 60-90 kg. Inclusion criteria: the presence of polypous rhinosinusitis (J33) in combination with bronchial asthma with a predominance of the allergic component (J45.0), mild to moderate severity, persistent form, uncontrolled course. The effectiveness of recombinant antibody to immunoglobulin E was evaluated at 3 rd , 4 th and 5 th months compared with groups that received only standard basic complex therapy. Results and discussion. In patients with polypous rhinosinusitis accompanied by bronchial asthma receiving the recombinant antibody to immunoglobulin IgE: nasal respiration was restored by 63%, 66.2% and 68.9%, olfactory improvement by 52%, 63.5% and 67.9% on the 3 rd , 4 th and 5 th month of therapy, respectively. According to CT data, at the end of the 5 th month of therapy, 70% of patients had a polypous process of 0-5 points, 30% of patients had values of 6-10 points of Lund-Mackay staging. According to the SF-36 questionnaire, normalization of quality-of-life indicators was recorded in the form of improved role functioning, vital activity and emotional state by 33.6, 33.3 and 30.2 points, respectively. The subjects receiving conservative therapy did not experience any allergic reactions or side effects during treatment. Conclusions. The leading clinical manifestations of persistent atopic bronchial asthma, allergic rhinitis, nasal polyposis, and chronic idiopathic urticaria are nasal obstruction, rhinorrhea, hyperemia, and itching of the skin. These symptoms are caused by premature release of inflammatory mediators, the main one being histamine. The use of targeted therapy with humanized monoclonal antibodies is more likely to control the cascade of symptoms in patients with diseases refractory to H1 blockers.
Background. Cervical cancer (CC) is among the four most common malignancies among the female population. For a long time, platinum-based chemotherapy was the standard of care and practically the only option available. However, treatment outcomes for patients with metastatic and recurrent CC remained poor. The use of immune checkpoint inhibitors significantly increased progression-free survival and overall survival in this group of patients. Currently, pembrolizumab is a priority option in treating patients with metastatic, persistent, recurrent CC with CPS ≥ 1 and is included in international and Russian clinical guidelines. Aim. To evaluate the efficacy and safety of a pembrolizumab biosimilar (Pembroria®) in patients with metastatic, persistent and recurrent CC in the interim analysis of the PERFECTION observational study. Materials and methods. The study included a group of 51 patients diagnosed with stage IV CC. The treatment efficacy was analyzed using the Fleming method with the objective response rate criterion according to RECIST 1.1. Safety was assessed by the incidence of adverse events (AEs) and serious AEs according to the CTCAE 5.0 toxicity scale. Results. At stage g2, an objective response was reported in 24 (47.1%) patients, which exceeded the target threshold (22 responses). 5 (9.8%) patients experienced immune-mediated AEs, a total of 6 cases, including 1 case of grade 3 AE. The overall objective response rate was consistent with KEYNOTE-826, but the AE rate was lower (34.5% in KEYNOTE-826). Conclusion. Pembroria® has demonstrated efficacy comparable to that of the original pembrolizumab product and an acceptable safety profile. Differences in the incidence of immune-mediated AEs associated with Pembroria® require further study, considering the duration of observation and sample size. The results support using Pembroria® in routine clinical practice.
