RESUMO
BACKGROUND: Limited data exists on the efficacy of immune checkpoint inhibitor (ICI) combinations in non-small-cell lung cancer (NSCLC) with uncommon driver alterations in genes such as ERBB2, BRAF, RET, and MET. This study retrospectively assessed ICI-combination therapy outcomes in this molecular subset of NSCLC. METHODS: We retrospectively analyzed patients with advanced NSCLC confirmed with driver alterations in genes including ERBB2, BRAF, RET or MET, and received ICI combined with chemotherapy (ICI + chemo) and/or targeted therapy (ICI + chemo/TT) as first-line (1L) or second- or third-line (≥ 2L) treatment at Hunan Cancer Hospital between January 2018 and May 2024. RESULTS: Of the 181 patients included in the study, 131 patients received 1L-ICI + chemo (ERBB2, n = 64; BRAF, n = 34; RET, n = 23; and MET, n = 10), and 50 patients received ≥ 2L-ICI + chemo/TT (ERBB2, n = 16; BRAF, n = 7; RET, n = 14; MET, n = 13). The full cohort had an overall response rate (ORR) of 45.9% and disease control rate of 84.0%. Among patients who received 1L-ICI + chemo, ORR ranged between 51.6% and 60.0%, with the median progression-free survival (mPFS) and overall survival (mOS) of 8.2 and 21.0 months for those with ERBB2-altered tumors, 10.0 and 15.0 months for BRAF-altered tumors, 12.1 months and OS not reached for RET-altered tumors, and 6.2 and 28.0 months for MET-altered tumors, respectively. Additionally, ORR ranged between 14.3% and 30.8% for ≥ 2L-ICI + chemo/TT; mPFS and mOS were 5.4 and 16.2 months for patients with ERBB2-altered tumors, 2.7 and 5.0 months for BRAF-altered tumors, 6.2 and 14.3 months for RET-altered tumors, and 5.7 and 11.5 months for MET-altered tumors, respectively. CONCLUSION: ICI-based combination therapies, regardless of treatment line, were effective in treating patients with advanced NSCLC harboring driver alterations in ERBB2, BRAF, RET, or MET. This suggests their potential as alternative treatment options in this patient population.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Receptor ErbB-2 , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Idoso de 80 Anos ou mais , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-ret/genética , Resultado do Tratamento , Mutação , Proteínas Proto-Oncogênicas c-met/genéticaRESUMO
INTRODUCTION: KRAS is the most frequently mutated oncogene in cancer and encodes a key signaling protein in tumors. Due to its high affinity for GTP and the lack of a large binding pocket that allosteric inhibitors can occupy, KRAS has long been considered 'non-druggable.' Finding effective treatment measures for patients with KRAS mutations is our top priority. AREAS COVERED: In this article, we will provide an overview of the KRAS pathway and review the current state of therapeutic strategies for targeting oncogenic KRAS, as well as their potential to improve outcomes in patients with KRAS-mutant malignancies. We will also discuss the development of these strategies and gave an outlook on prospects. EXPERT OPINION: KRAS mutations have posed a significant challenge in the treatment of advanced non-small cell lung cancer (NSCLC) over the past few decades. However, the emergence of immunotherapy and KRAS inhibitors, such as Sotorasib (AMG 510) and Adagrasib (MRTX849), has marked a new era in cancer therapy. As more research and clinical trials continue, we anticipate the development of more effective treatment strategies and better options for lung cancer patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , MutaçãoRESUMO
OBJECTIVE: To investigate the effects of Compound Xuanju Capsule on the levels of sex hormones and the weight of sexual organs in castrated male rats. METHODS: A randomized model control trail was performed in 60 young male SD rats of SPF grade, of which 12 were included in the normal control group, and the others were castrated and randomly divided into a model control group and a high-dose, a median-dose and a low-dose Xuanju group. The control groups received intragastric administration of normal saline, and the model groups solution of Compound Xuanju Capsule, all for 20 days. Then we determined by radioimmunoassay the levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the peripheral blood of the rats, and measured the weights of the epididymis, preputial gland, seminal vesicle, prostate and levator ani muscle. RESULTS: The T levels were remarkably lower in the castrated groups than in the normal controls, and significantly higher in the three Xuanju groups than in the model controls (P < 0.01). Both LH and FSH levels were increased in the model control and Xuanju groups as compared with the normal control group, the former with statistically significant difference (P < 0.05) and the latter without. In comparison with the normal controls, the model control rats showed a marked reduction in the indexes of the preputial gland, seminal vesicle, prostate and levator ani muscle, and the high-dose Xuanju group exhibited a significant increase in the seminal vesicle index as compared with the model controls (P < 0.05). There were no statistically significant differences in the indexes of preputial gland, prostate and levator ani muscle among different dose groups (P > 0.05). CONCLUSION: Compound Xuanju Capsule can elevate T and LH levels in the peripheral blood of male SD rats and improve the indexes of their sex organs, which may be an important mechanism behind its effect on ED.