scholarly journals Durable Response to the Combination of Atezolizumab With Platinum-Based Chemotherapy in an Untreated Non-Smoking Lung Adenocarcinoma Patient With BRAF V600E Mutation: A Case Report

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaomin Niu ◽  
Yingjia Sun ◽  
David Planchard ◽  
Luting Chiu ◽  
Jian Bai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Nsclc Patient ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Braf V600e ◽  
First Line ◽  
Liquid Biopsies ◽  
Durable Response ◽  
Platinum Based Chemotherapy ◽  
Lung Adenocarcinoma Patient

BackgroundImmune checkpoint inhibitor (ICPi) has become a major treatment in advanced non-small cell lung cancer (NSCLC) and demonstrated a clinical benefit for NSCLC patients with high programmed death ligand-1 (PD-L1) expression without EGFR/ALK/ROS1 drivers; however, the benefit in BRAF V600E NSCLC is so far unknown. Here, we report a case of prolonged tumor response to the combination of immunotherapy with chemotherapy in a non-smoking BRAF V600E NSCLC patient.Materials and MethodsWe verify a co-expression of BRAF V600E mutation and PD-L1 high expression more than 50% on formalin-fixed paraffin-embedded tumor sample of a newly diagnosed lung adenocarcinoma patient by immunohistochemistry and BRAF V600E/EGFR/ALK/ROS1 Mutations Detection Kit. The tissue and liquid biopsies were further subjected to next-generation sequencing (NGS) for identification of mutations with progression on immunotherapy and BRAF inhibitor (BRAFi). The patient had provided written informed consent and authorized the publication of clinical case.ResultsWe demonstrate the case of 62-year-old female non-smoker with high PD-L1 expression and BRAF V600E mutated NSCLC. The progression-free survival (PFS) of first-line combination of atezolizumab with platinum-based chemotherapy and sequential second-line treatment with BRAFi Vemurafenib are 20 and 5.5 months, respectively.ConclusionThis case shows a durable response to ICPi in BRAF V600E non-smoking lung adenocarcinoma with PFS of 20 months under first-line atezolizumab plus chemotherapy treatment. The case supports the idea that the combination immunotherapy may be an attractive option for BRAF V600E mutated non-smoking NSCLC with high PD-L1 expression.

scholarly journals Vasculogenic mimicry, a negative indicator for progression free survival of lung adenocarcinoma irrespective of first line treatment and epithelial growth factor receptor mutation status

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuejun He ◽  
Jijun You ◽  
Haibing Ding ◽  
Zhisheng Zhang ◽  
Lin Cui ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Target Therapy ◽  
Vasculogenic Mimicry ◽  
Therapy Response ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Abstract Background Vascular mimicry (VM) was associated with the prognosis of cancers. The aim of the study was to explore the association between VM and anticancer therapy response in patients with lung adenocarcinoma. Methods This was a single-center retrospective study of patients with lung adenocarcinoma between March 1st, 2013, to April 1st, 2019, at the Second People’s Hospital of Taizhou City. All included patients were divided into the VM and no-VM groups according to whether VM was observed or not in the specimen. Vessels with positive PAS and negative CD34 staining were confirmed as VM. The main outcome was progression-free survival (PFS). Results Sixty-six (50.4%) patients were male. Eighty-one patients received chemotherapy as the first-line treatment, and 50 patients received TKIs. Forty-five (34.4%) patients were confirmed with VM. There was no difference regarding the first-line treatment between the VM and no-VM groups (P = 0.285). The 86 patients without VM had a median PFS of 279 (range, 90–1095) days, and 45 patients with VM had a median PFS of 167 (range, 90–369) days (P < 0.001). T stage (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.10–1.71), N stage (HR = 1.43, 95%CI: 1.09–1.86), M stage (HR = 2.85, 95%CI: 1.76–4.61), differentiation (HR = 1.85, 95%CI: 1.29–2.65), therapy (HR = 0.32, 95%CI: 0.21–0.49), VM (HR = 2.12, 95%CI: 1.33–3.37), and ECOG (HR = 1.41, 95%CI: 1.09–1.84) were independently associated with PFS. Conclusion The benefits of first-line TKIs for NSCLC with EGFR mutation are possibly better than those of platinum-based regimens in patients without VM, but there is no difference in the benefit of chemotherapy or target therapy for VM-positive NSCLC harboring EGFR mutations.

scholarly journals Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 434 ◽  
Author(s):  
Ming-Ju Tsai ◽  
Jen-Yu Hung ◽  
Mei-Hsuan Lee ◽  
Chia-Yu Kuo ◽  
Yu-Chen Tsai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line ◽  
Free Survival ◽  
Younger Patients ◽  
Epidermal Growth

Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.

scholarly journals Efficacy of First-Third generation EGFR inhibitor combined with chemotherapy as first-line treatment for advanced lung adenocarcinoma in a real-world setting

2021 ◽  
Author(s):  
Ming-Wei Chen Ming-Wei Chen ◽  
An-Tai He . ◽  
Yi Pei .
Keyword(s):  
Lung Adenocarcinoma ◽  
Survival Time ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Combination Group ◽  
First Line ◽  
Free Survival ◽  
Mean Survival Time ◽  
First Line Therapy ◽  
To Receive

Abstract BackgroundTo explore the optimal treatment strategy for patients who harbor sensitive EGFR mutations, a head-to-head study was performed to compare chemotherapy and gefitinib-erlotinip, osimertinib treatment in combination or with either agent alone as first-line therapy, in terms of efficacy and safety.MethodsA total of 200 untreated patients with advanced lung adenocarcinoma who harbored sensitive EGFR mutations were randomly assigned to receive gefitinib-erlotinip combined with pemetrexed and carboplatin group, gefitinib-erlotinip osimertinib combined with pemetrexed and carboplatin group, pemetrexed plus carboplatin alone group, or gefitinib-erlotinip alone group, osimertinib alone group.ResultsThe progression-free survival (PFS) of patients in the gefitinib-erlotinip combination group Mean Survival Time PFS 22.00 month,95%CI[16.29,27.70] and osimertinib gefitinib-erlotinip combination group Mean Survival Time PFS 40.00 month,95%CI[28.12,51.87]was longer than that of patients in the chemotherapy alone group PFS10,81 months, 95% CI,[ 8.99–12.64],gefitinib-erlotinip alone group PFS14.00 month.95%CI[11.98-20.01], osimertinib alone group PFS 26.66 month 95%CI[24.77-29.22].The gefitinib-erlotinip osimertinib combinational resulted in longer overall survival (OS) than chemotherapy alone (HR = 0.46, p = 0.016) or gefitinib-erlotinip alone (HR = 0.36, p = 0.01). osimertinib alone (HR = 0.26, p = 0.01).ConclusionsOur finding suggested that treatment with pemetrexed plus carboplatin combined with gefitinib-erlotinip and pemetrexed plus carboplatin combined with gefitinib-erlotinip osimertinib group could provide better survival benefits for patients with lung adenocarcinoma harboring sensitive EGFR mutations.

The prognostic impact of bone metastasis in urothelial carcinoma treated with first-line platinum-based chemotherapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 415-415
Author(s):  
Husam Alqaisi ◽  
Zachary William Neil Veitch ◽  
Carlos Stecca ◽  
Jeenan Kaiser ◽  
Scott A. North ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Performance Status ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Prognostic Impact ◽  
First Line ◽  
Ecog Performance Status ◽  
Cancer Centre ◽  
Platinum Based Chemotherapy ◽  
Line Setting

415 Background: Metastatic urothelial carcinoma (mUC) is an aggressive disease with a median overall survival (OS) of ≈ 15 months. In the first-line setting, key prognostic factors include ECOG performance status, white blood cell count, and response to treatment per the Galsky nomogram. Bone metastases (BM) in mUC are associated with morbidity and mortality but are grouped with visceral disease; hence, their impact on prognosis is not well established. We aimed to assess the survival impact of BM in mUC patients treated with first-line platinum-based chemotherapy (PBC). Methods: A retrospective collection of patient and tumor characteristics, with clinical response to treatment (complete response [CR], partial response [PR]; stable disease [SD] or progressive disease [PD]) for patients treated at Princess Margaret Cancer Centre, Tom Baker Cancer Centre, and Cross Cancer Institute from 2005-2018 was performed. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method. Univariate (UVA) followed by multivariate analysis (MVA) of patient variables [Cox] using PFS and OS was performed. Results: Overall 376 mUC patients were included; 222 (59%) had soft-tissue metastases (STM) only, 70 (19%) had bone-only metastases, and 84 (22%) had both STM and BM. Overall, 35% had PR or CR, 19% had SD, and 39% had PD (7%: unknown response). The median PFS and OS for the whole cohort were 5.6 months (95%CI: 4.8-6.4) and 9.7 months (95% CI: 8.8-10.8) respectively. Select UVA by metastatic site showed inferior PFS for bone-only (p=0.03) and combination STM and BM (p=0.017). Only combination STM and BM were significant on UVA for OS (p=0.002). MVA showed that bone-only metastases (p=0.03) and ECOG 3-4 (p<0.0001) were associated with worse PFS (Table). Predictors of worse OS were the combination of STM and BM (p=0.02), ECOG 3-4 (p=0.001), and WBCs ≥ULN (p=0.02), (Table). Conclusions: BM are a significant predictor of worse outcomes for mUC patients treated with first-line PBC. Consideration as a treatment stratification factor for future studies is suggested. Strategies for the treatment of mUC patients with BM (ie: bone targeted agents) in the first-line setting should be addressed in future trials. [Table: see text]

scholarly journals KRAS Mutations Predict Response and Outcome in Advanced Lung Adenocarcinoma Patients Receiving First-Line Bevacizumab and Platinum-Based Chemotherapy

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1514 ◽  
Author(s):  
Ghimessy ◽  
Gellert ◽  
Schlegl ◽  
Hegedus ◽  
Raso ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kras Mutation ◽  
Antiangiogenic Therapy ◽  
Hazard Ratio ◽  
Wild Type ◽  
First Line ◽  
Kras Mutations ◽  
Exon 2 ◽  
Mutational Status ◽  
Platinum Based Chemotherapy

Bevacizumab, combined with platinum-based chemotherapy, has been widely used in the treatment of advanced-stage lung adenocarcinoma (LADC). Although KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation is the most common genetic alteration in human LADC and its role in promoting angiogenesis has been well established, its prognostic and predictive role in the above setting remains unclear. The association between KRAS exon 2 mutational status and clinicopathological variables including progression-free survival and overall survival (PFS and OS, respectively) was retrospectively analyzed in 501 Caucasian stage IIIB-IV LADC patients receiving first-line platinum-based chemotherapy (CHT) with or without bevacizumab (BEV). EGFR (epidermal growth factor receptor)-mutant cases were excluded. Of 247 BEV/CHT and 254 CHT patients, 95 (38.5%) and 75 (29.5%) had mutations in KRAS, respectively. KRAS mutation was associated with smoking (p = 0.008) and female gender (p = 0.002) in the BEV/CHT group. We found no difference in OS between patients with KRAS-mutant versus KRAS wild-type tumors in the CHT-alone group (p = 0.6771). Notably, patients with KRAS-mutant tumors demonstrated significantly shorter PFS (p = 0.0255) and OS (p = 0.0186) in response to BEV/CHT compared to KRAS wild-type patients. KRAS mutation was an independent predictor of shorter PFS (hazard ratio, 0.597; p = 0.011) and OS (hazard ratio, 0.645; p = 0.012) in the BEV/CHT group. G12D KRAS-mutant patients receiving BEV/CHT showed significantly shorter PFS (3.7 months versus 8.27 months in the G12/13x group; p = 0.0032) and OS (7.2 months versus 16.1 months in the G12/13x group; p = 0.0144). In this single-center, retrospective study, KRAS-mutant LADC patients receiving BEV/CHT treatment exhibited inferior PFS and OS compared to those with KRAS wild-type advanced LADC. G12D mutations may define a subset of KRAS-mutant LADC patients unsuitable for antiangiogenic therapy with BEV.

scholarly journals Outcomes of BRAF V600E Pediatric Gliomas Treated With Targeted BRAF Inhibition

2020 ◽  
pp. 561-571 ◽  
Author(s):  
Liana Nobre ◽  
Michal Zapotocky ◽  
Vijay Ramaswamy ◽  
Scott Ryall ◽  
Julie Bennett ◽  
...  
Keyword(s):  
Objective Response ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Homozygous Deletion ◽  
Braf V600e ◽  
Rapid Progression ◽  
Low Grade ◽  
Term Survival ◽  
Braf Inhibition ◽  
Poor Outcomes

PURPOSE Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors. PATIENTS AND METHODS We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E–mutated glioma treated with BRAF inhibition across 29 centers from multiple countries. RESULTS Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy ( P < .001). These responses were rapid (median, 4 months) and sustained in 86% of tumors up to 5 years while receiving therapy. After discontinuation of BRAF inhibition, 76.5% (13 of 17) of patients with PLGG experienced rapid progression (median, 2.3 months). However, upon rechallenge with BRAF inhibition, 90% achieved an objective response. Poor prognostic factors in conventional therapies, such as concomitant homozygous deletion of CDKN2A, were not associated with lack of response to BRAF inhibition. In contrast, only 36% of those with PHGG responded to BRAF inhibition, with all but one tumor progressing within 18 months. In PLGG, responses translated to 3-year progression-free survival of 49.6% (95% CI, 35.3% to 69.5%) versus 29.8% (95% CI, 20% to 44.4%) for BRAF inhibition versus chemotherapy, respectively ( P = .02). CONCLUSION Use of BRAF inhibition results in robust and durable responses in BRAF V600E–mutated PLGG. Prospective studies are required to determine long-term survival and functional outcomes with BRAF inhibitor therapy in childhood gliomas.

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