Clinical characteristics and treatment outcomes of 65 patients with BRAF-mutated non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21745-e21745
Author(s):  
Yuxin Mu ◽  
Ke Yang ◽  
Xuezhi Hao ◽  
Yan Wang ◽  
Lin Wang ◽  
...  

e21745 Background: BRAF mutations are infrequently seen in non-small cell lung cancer (NSCLC) in Chinese population. We aimed to investigate the clinicopathologic characteristics and treatment outcomes of Chinese patients with NSCLC harboring BRAF mutations. Methods: We conducted a retrospective multicenter study in China of patients with NSCLC harboring BRAF mutations between Jan 2017 and Jul 2019. Results: A total of 65 patients treated in 22 centers were included, 54 harbored BRAF-V600E mutation and 11 had non-V600E mutations, including K601E, G469S, G469V, G469A, G596R, G466R and T599dup. No significant difference in age or gender was found between BRAF-V600E and non-V600E cases, while the majority of patients with non-V600E mutations were smokers (81.8%). Of the 18 patients with early-stage disease at diagnosis and underwent a resection, the median disease-free survival (DFS) was 43.2 months, 18.7 months and 10.1 months of stage I, II and IIIA patients (P = 0.07), respectively. In 46 patients with advanced-stage disease at data cutoff, disease control rate (DCR) and progression-free survival (PFS) of first-line anti-BRAF targeted therapy was superior than chemotherapy in patients harboring BRAF-V600E mutation (DCR, 100.0% vs. 70.0%, P = 0.027; median PFS, 9.8 months vs. 5.4 months, P = 0.149). Of 30 V600E-mutated patients who received anti-BRAF therapy during the course of disease, the median PFS of vemurafenib, dabrafenib, and dabrafenib plus trametinib was 7.8 months, 5.8 months and 6.0 months, respectively (P = 0.970). Median PFS were similar between V600E and non-V600E patients (5.4 months vs. 5.4 months, P = 0.825) to first-line chemotherapy. Nine patients were treated with checkpoint inhibitors, DCR and median PFS were 62.5% and 3.0 months (95%CI 2.9, 3.1), respectively. Conclusions: Our data demonstrated the clinical benefit of anti-BRAF targeted therapy in Chinese NSCLC patients harboring BRAF-V600E mutation. The value of immunotherapy and treatment selection among non-V600E population needs further study.[Table: see text]

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangyun Liu ◽  
Yixuan Zhang ◽  
Miaowen Liu ◽  
Ruoxin Xu ◽  
Fengming Yi ◽  
...  

Abstract Background Although pembrolizumab has shown clinical benefit in patients with small-cell lung cancer (SCLC), its actual efficacy in combination with a conventional chemotherapy drug has not been determined. We performed this study to discern the efficacy and risk of pembrolizumab in combination with chemotherapy as first-line therapy in SCLC patients. Methods We systematically searched the PubMed, ScienceDirect, Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar databases for relevant studies. The main outcomes were overall survival (OS) and progression-free survival (PFS). Results We identified 2980 articles and included 6 studies (5 were noncomparative open-label studies and 1 was a randomized controlled trial [RCT]) involving 396 patients in our meta-analysis. The pooled median OS (mOS) was 9.6 months (95% CI, 8.0-11.2), and the pooled median PFS (mPFS) was 4.2 months (95% CI, 2.2-6.1). The 1-year overall survival rate (OSR-1y) and 6-month progression-free survival rate (PFSR-6m) were 45.1% (95% CI, 33-57.2%) and 41.6% (95% CI, 24.3-59%), respectively. The objective response rate (ORR) was 38.8% (95% CI, 11.9-65.67%), disease control rate (DCR) was 69.30% (95% CI, 51.6-87.0%), complete response (CR) was 2.20% (95% CI, 0.8-3.7%), partial response (PR) was 34.70% (95% CI, 7.8-61.5%), and stable disease (SD) was 20.90% (95% CI, 9.1-32.6%). The grade 3-4 adverse effect (AE) rate was 20.88% (95% CI, 1.22-54.85%). The most common AEs were neutropenia (90.16%), anemia (53.21%), dysphagia (41.96%), platelet count decrease (34.87%), and esophagitis (32.89%); severe AEs included neutropenia, respiratory failure, pneumonitis, acute coronary syndrome, and colitis/intestinal ischemia. Conclusions The combination of pembrolizumab with conventional chemotherapy is an effective therapeutic schedule with acceptable and manageable efficacy and toxicity in patients with SCLC. More high-quality and well-designed RCTs with large sample sizes are warranted to further validate our findings.


Oncology ◽  
2020 ◽  
Vol 98 (11) ◽  
pp. 749-754 ◽  
Author(s):  
Venu Madhav Konala ◽  
Bhaskar Reddy Madhira ◽  
Sara Ashraf ◽  
Stephen Graziano

Lung cancer is a leading cause of cancer death in the United States and around the world. Approximately 13% of lung cancers are small cell lung cancer (SCLC). SCLC is generally classified as a limited-stage and extensive-stage disease depending on the extent of involvement. For patients with the extensive-stage disease, until recently, chemotherapy alone has been the recommended treatment, although radiotherapy could be used in select patients for palliation of symptoms. The standard of care for extensive-stage SCLC is platinum doublet chemotherapy with either cisplatin or carboplatin in combination with etoposide. Even though first-line therapy has an initial response rate of 60–80%, the prognosis is poor, with overall survival of 10–12 months. The only FDA-approved second line of therapy is topotecan, approved both as an intravenous formulation as well as an oral formulation, with response rates of 6–12% in chemorefractory disease and 15–37% in chemosensitive disease. Immunotherapy has recently been approved as a first-line agent in metastatic SCLC in combination with chemotherapy. It is also approved as a third-line agent in metastatic SCLC after the failure of two chemotherapy regimens. The FDA approved four drugs, two of them being PD-1 inhibitors (pembrolizumab, nivolumab), and two of them being PD-L1 inhibitors (atezolizumab and durvalumab) in SCLC. This review article summarizes the significance of immunotherapy in the treatment of extensive-stage SCLC, its side effects, and limitations.


2019 ◽  
Vol 26 (2) ◽  
pp. 1117-1128 ◽  
Author(s):  
Márton Szentkereszty ◽  
Zsolt István Komlósi ◽  
Gergő Szűcs ◽  
Gábor Barna ◽  
Lilla Tamási ◽  
...  

2007 ◽  
Vol 25 (36) ◽  
pp. 5777-5784 ◽  
Author(s):  
Charles A. Butts ◽  
David Bodkin ◽  
Edward L. Middleman ◽  
Craig W. Englund ◽  
David Ellison ◽  
...  

PurposeTo evaluate the efficacy of cetuximab added to first-line gemcitabine/platinum in chemotherapy-naïve patients with advanced non–small-cell lung cancer (NSCLC).Patients and MethodsIn this noncomparative, randomized trial, chemotherapy-naïve patients with recurrent/metastatic NSCLC (stage IV or stage IIIB with malignant pleural effusion) were eligible. Patients received cisplatin (75 mg/m2IV, every 3 weeks) or carboplatin (area under the concentration-versus-time curve of 5 intravenously [IV], every 3 weeks), and gemcitabine (1,250 or 1,000 mg/m2IV, days 1 and 8) plus cetuximab (400 mg/m2IV day 1, followed by 250 mg/m2weekly), in arm A, or chemotherapy alone, in arm B. Response rate was the primary end point; safety, progression-free survival, and overall survival were secondary end points.ResultsSixty-five patients were randomly assigned to arm A and 66 to arm B. Partial responses were observed in 18 patients (27.7%; 95% CI, 17.3 to 40.2) in arm A and 12 (18.2%; 95% CI, 9.8 to 29.6) in arm B. Median progression-free survival was 5.09 months for arm A (95% CI, 4.17 to 5.98) and 4.21 months (95% CI, 3.81 to 5.49) in arm B. Median overall survival was 11.99 months (95% CI, 8.80 to 15.18) and 9.26 months (95% CI, 7.43 to 11.79) in arms A and B, respectively. Overall toxicity was acceptable and consistent with the profiles of the individual agents.ConclusionFirst-line treatment with cetuximab plus gemcitabine/platinum is well tolerated and can be administered safely in patients with advanced NSCLC. Differences in response rate, progression-free survival, and overall survival suggest that the addition of cetuximab to platinum/gemcitabine may improve clinical outcomes. Larger studies are in progress to address this hypothesis.


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