scholarly journals Sequential Treatment of Afatinib and Osimertinib in Patients with Advanced Non-small Cell Lung Cancer Harboring EGFR Mutations: Results from a Real-world Study in South Korea

2021 ◽  
Author(s):  
Taeyun Kim ◽  
Tae Won Jang ◽  
Chang Min Choi ◽  
Mi-Hyun Kim ◽  
Sung Yong Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
South Korea ◽  
Small Cell Lung Cancer ◽  
Survival Rates ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Group A ◽  
Group B ◽  
Egfr Mutated

Abstract The optimal sequence for administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for treating non-small cell lung cancer (NSCLC) is still unclear. This study aimed to evaluate the efficacy of sequential afatinib and osimertinib treatment in patients with NSCLC harboring EGFR mutations. Electronic records of patients with EGFR-mutated NSCLC, who were administered afatinib and osimertinib (group A) or other chemotherapy (group B) between October 2014 and October 2019, across 16 hospitals in South Korea were reviewed. The primary outcome, time on treatment (TOT), secondary outcome, and overall survival (OS) were estimated using the Kaplan-Meier method and log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. Of the 737 patients who received frontline afatinib treatment, 360 with complete records were selected (group A:154, group B: 206). The median TOT was 33.9 months (95% confidence interval [CI]: 24.5−43.3) in group A and 21.3 months (95% CI: 19.4−23.1) in group B. The median TOT with afatinib was 12.9 months (95% CI: 11.8−14.0) overall, and 15.2 months (95% CI: 13.2−17.1) in group A. The 2- and 3-year survival rates were 86.0% and 69.3% in group A and 75.9% and 55.3% in group B, respectively. Sequential afatinib and osimertinib treatment resulted in better survival rates than treatment with afatinib followed by other chemotherapies. Therefore, this sequential treatment strategy may offer clinical benefits to patients with EGFR-mutated NSCLC.

Response with pemrbolizumab in a patient with EGFR mutated non-small cell lung cancer harbouring insertion mutations in V834L and L858R

2021 ◽  
pp. 107815522110578
Author(s):  
Matthew J. Hadfield ◽  
Alla Turshudzhyan ◽  
Khalid Shalaby ◽  
Aswanth Reddy
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Durable Response ◽  
Egfr Mutated

Introduction Lung cancer is the leading cause of cancer-related deaths with non-small cell lung cancer (NSCLC) being the most common of them. About a third of NSCLC cases have an epidermal growth factor (EGFR) mutation, which is usually susceptible to tyrosine kinase inhibitors (TKIs). In rare cases where patients progress through TKI therapy, the use of immune checkpoint inhibitors (ICIs) remains controversial. Case report We describe a case of a patient with significant history of smoking and EGFR mutated programmed death ligand-1 (PD-L1) positive NSCLC who was initially treated with TKI therapy. Management/Outcome While patient progressed on TKI therapy, he was able to achieve a durable response with a single PD-L1 agent, pembrolizumab. Contrary to the available evidence, the presented EGFR mutant NSCLC responded to PD-L1 pathway inhibition. Discussion From our observation Pembrolizumab could be promising in patients with rare EGFR mutations who do not respond to EGFR directed therapy. Our report provides supporting data for the use of immunotherapies in patients with EGFR mutated NSCLC.

scholarly journals Characteristics of non-small-cell lung cancer with interstitial pneumonia: variation in cancer location, histopathology, and frequency of postoperative acute exacerbations in interstitial pneumonia

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Kazumasa Ogawa ◽  
Hironori Uruga ◽  
Takeshi Fujii ◽  
Sakashi Fujimori ◽  
Tadasu Kohno ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Interstitial Pneumonia ◽  
Squamous Cell ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Acute Exacerbations ◽  
Group A ◽  
Group B

Abstract Background Non–small-cell lung cancer (NSCLC) has been reported to develop in patients with interstitial pneumonia (IP); however, clinical, radiological, and pathological features remain to be elucidated. Methods We retrieved the records of 120 consecutive NSCLC patients associated with IP who underwent surgery at Toranomon Hospital between June 2011 and May 2017. We classified the patients into three groups according to NSCLC location using high-resolution computed tomography: group A, within a fibrotic shadow and/or at the interface of a fibrotic shadow and normal lung; group B, within emphysematous tissue and/or at the interface of emphysematous tissue and normal lung; and group C, within normal lung. In 64 patients, programmed death ligand-1 (PD-L1) status was assessed with immunohistostaining. Results Most of the patients (89; 70%) were classified as group A. This group tended to have squamous cell carcinoma with the usual interstitial pneumonia (UIP). These cancers were located mainly in the lower lobes and seven of the eight postoperative acute exacerbations (pAE) of IP developed in this group. NSCLC in the group B were mainly squamous cell carcinomas located in the upper lobes. No patient with PD-L1 negative was classified into group B. None of the patients in group C showed UIP. and most of the cancers were adenocarcinoma. The frequency of epidermal growth factor receptor mutation-positive NSCLC was the highest in this group. Conclusions The three groups each showed characteristic features in terms of tumor location, histopathology, PD-L1 expression, and frequency of pAEof IP.

The effect of nivolumab treatment for central nervous system metastases in non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20601-e20601 ◽  
Author(s):  
Hiromi Watanabe ◽  
Toshio Kubo ◽  
Takashi Ninomiya ◽  
Kadoaki Ohashi ◽  
Eiki Ichihara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Central Nervous System ◽  
Nervous System ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Group A ◽  
Group B ◽  
Nsclc Patients ◽  
Cns Lesions

e20601 Background: Central nervous system (CNS) metastases (mets) occur in 30% of patients with advanced non-small cell lung cancer (NSCLC) and are associated with poor overall survival (OS). Although nivolumab, a programmed death-1 immune checkpoint inhibitor antibody, has demonstrated a longer survival benefit compared with docetaxel in previously treated NSCLC patients (CheckMate 017 and 057; N Engl J Med, 2015), patients with symptomatic or untreated CNS mets were excluded in these trials. In CheckMate 012 Arm M, 2 of 12 patients (16.7%) with untreated CNS mets showed intracranial responses, but the effect of nivolumab treatment for CNS mets was not fully investigated. Methods: To investigate the effect and safety of nivolumab for CNS mets in NSCLC patients, we retrospectively analyzed 48 patients with NSCLC who were treated with nivolumab from February 2016 to December 2016 at Okayama University Hospital. Results: Twenty-nine patients (60%) had no CNS lesions (group A) and 19 patients (40%) had brain mets (BM) (group B). In group B, 15 patients (79%) received radiotherapy (RT) for BM, including 5 patients who received RT just before nivolumab treatment. The responses of extra-CNS lesions to nivolumab are shown in the table. The PFS was longer in group A than in group B (p=0.14). In group B, the PFS of patients who received prior RT tended to be longer than in those without RT (p=0.42); OS was not reached in either group. In group B, the effects of nivolumab treatment for CNS mets were evaluated in 12 patients: SD occurred in 3 patients (25%), PD in 4 patients (33%), and NE in 5 patients (42%). All 4 patients with PD in the CNS lesion also showed PD in the extra-CNS lesion. In group A, no patients showed progression only in the CNS lesion. Conclusions: In this retrospective study, there were no patients treated only with nivolumab who showed a response to CNS mets. RT prior to nivolumab might be more effective, so future investigations should involve additional cases and prospective studies. [Table: see text]

Clinical Features and Outcome of Patients With Non–Small-Cell Lung Cancer Harboring BRAF Mutations

2011 ◽  
Vol 29 (26) ◽  
pp. 3574-3579 ◽  
Author(s):  
Antonio Marchetti ◽  
Lara Felicioni ◽  
Sara Malatesta ◽  
Maria Grazia Sciarrotta ◽  
Luigi Guetti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survival Rates ◽  
Multivariate Logistic Regression Analysis ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Braf Mutations ◽  
Clinicopathologic Parameters

Purpose To investigate the prevalence, distribution, and prognostic role of BRAF mutations in a large cohort of white patients with non–small-cell lung cancer (NSCLC). Patients and Methods A retrospective series of 1,046 NSCLCs—comprising 739 adenocarcinomas (ADCs) and 307 squamous cell carcinomas (SCCs)—was investigated for BRAF mutations. High-resolution melting analysis followed by sequencing and strip hybridization assay were used. All patients were also analyzed for KRAS and EGFR mutations. Results BRAF mutations were present in 36 ADCs (4.9%) and one SCC (0.3%; P = .001). Twenty-one of the mutations (56.8%) were V600E, and 16 (43.2%) were non-V600E. V600E mutations were significantly more prevalent in females (16 of 187 patients; 8.6%) than in males (five of 552 patients; 0.9%), as indicated by multivariate logistic regression analysis (hazard ratio [HR], 11.29; P < .001). V600E-mutated tumors showed an aggressive histotype characterized by micropapillary features in 80% of patients and were significantly associated with shorter disease-free and overall survival rates on both univariate (HR, 2.67; P < .001 and HR, 2.97; P < .001, respectively) and multivariate analyses (HR, 2.19; P = .011 and HR, 2.18; P = .014, respectively). All non-V600E mutations were found in smokers (P = .015) and were associated with neither clinicopathologic parameters nor prognosis. BRAF and EGFR were concomitantly mutated in two tumors. Conclusion We report for the first time to our knowledge that V600E and non-V600E BRAF mutations affect different patients with NSCLC. V600E mutations are significantly associated with female sex and represent a negative prognostic factor. In addition, we identified a number of other clinicopathologic parameters potentially useful for the selection of patients carrying BRAF mutations.

scholarly journals Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients

2019 ◽  
Vol 21 (1) ◽  
pp. 66
Author(s):  
Elisa Boldrin ◽  
Giorgia Nardo ◽  
Elisabetta Zulato ◽  
Laura Bonanno ◽  
Valentina Polo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Loss Of Heterozygosity ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Genetic Characteristics ◽  
Nsclc Patients ◽  
Egfr Mutated

Liquid biopsy is currently approved for management of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. However, one unanswered question is whether the rate of cell-free DNA (cfDNA)-negative samples is due to technical limitations rather than to tumor genetic characteristics. Using four microsatellite markers that map specific chromosomal loci often lost in lung cancer, we conducted a pilot study to investigate whether other alterations, such as loss of heterozygosity (LOH), could be detected in EGFR-negative cfDNA. We analyzed EGFR-mutated NSCLC patients (n = 24) who were positive or negative for EGFR mutations in cfDNA and compared the results with a second cohort of 24 patients bearing KRAS-mutated cancer, which served as a representative control population not exposed to targeted therapy. The results showed that in EGFR-negative post-tyrosine-kinase-inhibitor (TKI) cfDNAs, LOH frequency was significantly higher than in both pre- and post-TKI EGFR-positive cfDNAs. By contrast, no association between KRAS status in cfDNA and number of LOH events was found. In conclusion, our study indicates the feasibility of detecting LOH events in cfDNA from advanced NSCLC and suggests LOH analysis as a new candidate molecular assay to integrate mutation-specific assays.

The association between STK11/LKB1 and/or KEAP1 mutations and response to PD-1/PD-L1 inhibitors in patients with advanced non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21538-e21538
Author(s):  
Meagan Elizabeth Miller ◽  
Meera Patel ◽  
Sandra K. Althouse ◽  
Nasser H. Hanna ◽  
Hirva Mamdani
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Concurrent Chemotherapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Disease Characteristics ◽  
Clinical Databases ◽  
Group A ◽  
Group B

e21538 Background: Advanced non-small cell lung cancer (NSCLC) patients with tumors harboring STK11/LKB1 or KEAP1 mutations have inferior treatment outcomes when treated with PD-1/PD-L1 blockade, regardless of KRAS status, PD-L1 score, or TMB score (Skoulidis et al, Cancer Discovery 2018, ASCO abstract 102, 2019). Methods: Retrospective clinical databases from Indiana University and Karmanos Cancer Institute were queried to identify patients from 2008-2019 with advanced NSCLC treated with PD-1/PD-L1 monotherapy (group A) or concurrent chemotherapy + PD-1/PD-L1 inhibitors (group B) whose tumors harbored STK11/LKB1 and/or KEAP1 mutations. Patients were characterized by best response, progression of disease (PD) or non-PD (complete response (CR) + partial response (PR) + stable disease (SD)). Patient and disease characteristics, response, and duration of response (> vs. < 6 months) were recorded. Results: A total of 77 patients met the above criteria (55 in group A, 22 in group B). 52 of 55 patients in group A received prior chemo. Patient and disease characteristics and outcomes are summarized in the table. Conclusions: STK11/LKB1 and/or KEAP1 mutations are independent of PD-L1/TMB status, although most patients had PD-L1 of <1%. Nearly ½ of patients with STK11/LKB1 and/or KEAP1 mutations achieve at least SD with PD-1/PD-L1 inhibitor monotherapy and more than 50% of those with non-PD maintain that response status for > 6 mos. The frequency and duration of non-PD in this population is higher in patients receiving chemotherapy + PD-1/PD-L1 concomitantly. [Table: see text]

scholarly journals Post-Progression Survival Is Strongly Associated with Overall Survival in Patients Exhibiting Postoperative Relapse of Non-Small-Cell Lung Cancer Harboring Sensitizing EGFR Mutations

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 508
Author(s):  
Hisao Imai ◽  
Ryoichi Onozato ◽  
Maiko Ginnan ◽  
Daijiro Kobayashi ◽  
Kyoichi Kaira ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Performance Status ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Individual Patient Level ◽  
Egfr Mutated

Background and Objective: Patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitizing epidermal growth factor receptor (EGFR) mutations show a good response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). The subsequent treatments influence the evaluability of the efficacy of front-line therapy on overall survival (OS). Consequently, we evaluated the associations of relapse-free survival (RFS) and post-progression survival (PPS) with OS in patients who exhibited postoperative relapse of EGFR-mutated NSCLC. Materials and Methods: We analyzed the data of 35 patients with EGFR-mutated NSCLC who underwent complete resection between January 2007 and June 2019. The correlations of RFS and PPS with OS were evaluated at the individual patient level. Results: Linear regression and Spearman’s rank correlation analyses demonstrated that the PPS highly correlated with OS (r = 0.91, p < 0.05, R2 = 0.85), whereas the RFS weakly associated with OS (r = 0.36, p < 0.05, R2 = 0.25). Age and performance status at relapse were significantly associated with PPS. Conclusion: Overall, PPS was more strongly and significantly associated with OS than RFS. These results suggest that the OS of our cohort may be affected by treatments, besides postoperative relapse. However, larger-scale prospective studies are needed to confirm these results.

Thymidylate synthase polymorphisms and immunohistochemistry in non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11101-11101
Author(s):  
J. Stoehlmacher ◽  
E. Goekkurt ◽  
G. Hoeffken ◽  
R. Zinsky ◽  
F. Lynch ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Cell Lung Cancer ◽  
Staining Intensity ◽  
Small Cell ◽  
Small Cell Lung ◽  
Histological Subtypes ◽  
Group A ◽  
Group B

11101 Background: Recently, pemetrexed has been introduced into the treatment of non-small cell lung cancer (NSCLC). There's evidence that pemetrexed appears to be more efficient in non squamous NSCLC including adenocarcinoma (AC) and large cell carcinoma (LCC). TS represents a major target enzyme of pemetrexed. We evaluated the expression of TS among different histological types of NSCLC and its association with functional genetic polymorphisms of the TS gene. Methods: Archived tumor samples from 312 individuals with NSCLC were analyzed. Immunohistochemistry (IHC) was performed using a mouse monoclonal antibody to TS. TS stained sections were scored for cytoplasmic and nuclear localization. For each compartment, the tumor was evaluated for the estimated percentage of positive cells with the greatest intensity within the tumor. Intensity was scored on a scale of 0–4. A score of 3–4 was classified as high expression. Genotyping of TS-VNTR including the G/C SNP and TS1394del6 was performed by PCR based RFLP techniques. Genotypes supposed to be associated with low expression were grouped (group A: 2R/2R or 2R/3RC or 3RC/3RC + -6/-6) and compared to genotype groups associated with high expression (group B: 2R/3RG or 3RC/3RG or 3RG/3RG + -6/+6 or +6/+6). Results: IHC and polymorphisms could be performed successfully in 312 (100%) and 287 (92%), respectively. Distribution of histology was as follows: 50% AC, 42% squamous cell carcinoma (SCC), 3% LCC and 5% mixed or other histological subtypes. Group B genotypes were significantly more present in SCC than in AC (49% vs 23%, p=.002). Tumors with group B genotypes were more likely to display high nuclear staining intensity than group A tumors (30% vs. 17%, p=.077). A similar but not significant trend was seen for cytoplasmic staining intensity. There was no significant difference between histological subtypes of NSCLC with respect to TS protein expression. AC were more common than SCC to show a G1 differentiated tumors (8% vs 1%, p<.001). No difference between genotype groups were observed with respect to grading. Conclusions: TS polymorphisms are significantly associated with histology subtypes in NSCLC. These results represent a potential explanation for efficacy differences of pemetrexed in NSCLC and warrants further investigations. [Table: see text]

Prevalence of EGFR mutations in non-small cell lung cancer (NSCLC) smoker patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21015-e21015 ◽  
Author(s):  
Yann Izarzugaza ◽  
Manuel Domine ◽  
Federico Rojo ◽  
Victoria Casado ◽  
Ana Leon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20 ◽  
Egfr Mutated ◽  
Exon 19

e21015 Background: Mutations in the Epidermal Growth Factor Receptor (EGFR) predict a better response to tyrosine kinase inhibitors compared to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Previous studies in caucasian population have reported a frequency of EGFR mutation of 10-15%. The aim of this study is to analyze the prevalence of EGFR mutations in caucasian smoker patients with NSCLC. Methods: Prospective mutation testing in NSCLC patients included in our institution since October 2010 to January 2012 was performed on DNA obtained from available tumor tissue and cytologic samples, using ARMS-scorpion TheraScreen EGFR 29 Mutation Test Kit (Qiagen). Results: From 218 consecutive NSCLC diagnoses, 18 (8.25%) patients showed EGFR mutations: 6 (33.3%) exon 19 deletions, 9 (50%) exon 21 mutations (7 cases L858R and 2 cases L861Q) and 3 (16.6%) exon 20 insertions. In the EGFR-mutated patients, 13 (72.25%) were never-smoker and 5 (27.7%) were smoker (3 current-smoker and 2 former-smoker). The EGFR-mutated smoker population showed the following characteristics: 3 female, 2 male; 4 adenocarcinoma, one squamous cell carcinoma; 3 stage IV, 2 stage IA at diagnosis; 1 (20%) case EGFR deletion exon 19, 1 (20%) case insertion exon 20 and 3 patients (60%) mutation exon 21 (2, L858R and 1, L861Q). Conclusions: The EGFR mutation rate in NSCLC smoking patients in our referral area is superior (27.7%) than previously reported, reinforcing the importance of including EGFR mutation testing in NSCLC smoking population for the correct management of these patients.

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