scholarly journals PD-L1 expression and response to pembrolizumab in patients with EGFR-mutant non-small cell lung cancer

2020 ◽  
Vol 50 (5) ◽  
pp. 617-622
Author(s):  
Eriko Miyawaki ◽  
Haruyasu Murakami ◽  
Keita Mori ◽  
Nobuaki Mamesaya ◽  
Takahisa Kawamura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Poor Response ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Egfr Mutant

Abstract Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer is less likely to express programmed death-ligand 1 (PD-L1) than tumors with wild-type EGFR and is associated with poor response to pembrolizumab. To understand the relationship between EGFR mutation and PD-L1 expression in pembrolizumab response, we retrospectively evaluated the factors contributing to the high tumor proportion score in 155 EGFR-mutant non-small cell lung cancer cases and their associated response to pembrolizumab. Uncommon EGFR mutations were significantly associated with a PD-L1 tumor proportion score ≥ 50% compared to common EGFR mutations. The objective response rate to pembrolizumab of 14 patients was 36%, including 22% in patients with common EGFR mutations, 60% in patients with uncommon EGFR mutations and 75% in patients with both uncommon mutations and a PD-L1 tumor proportion score ≥ 50%. A PD-L1 tumor proportion score ≥ 50% was more frequent in non-small cell lung cancer patients harboring uncommon EGFR mutations and was associated with pembrolizumab efficacy.

scholarly journals Combination of Crizotinib and Osimertinib in T790M+ EGFR-Mutant Non-Small Cell Lung Cancer with Emerging MET Amplification Post-Osimertinib Progression in a 10-Year Survivor: A Case Report

2021 ◽  
pp. 477-482
Author(s):  
Miriam Blasi ◽  
Daniel Kazdal ◽  
Michael Thomas ◽  
Petros Christopoulos ◽  
Mark Kriegsmann ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Met Amplification ◽  
Egfr Mutant

Tyrosine kinase inhibitors (TKIs) represent the standard treatment for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The duration of the response is, however, limited in time owing to the development of resistance mechanisms to both first- and second-generation agents such as MET oncogene amplification. This report describes the successful results obtained with the combination of the third-generation TKI osimertinib with the multitargeted TKI and MET inhibitor crizotinib in a patient with EGFR-mutant NSCLC with emerging MET amplification with a tolerable toxicity profile.

Anti-PD-1 antibody monotherapy or anti-PD-1 antibody combination with chemotherapy treated non-small cell lung cancer (NSCLC) patients with EGFR mutation: A retrospective analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21691-e21691
Author(s):  
Shaorong Yu ◽  
Ran Hu ◽  
Meiqi Shi
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Objective Response ◽  
Small Cell ◽  
Combined Chemotherapy ◽  
Small Cell Lung ◽  
Egfr Mutant ◽  
Nsclc Patients

e21691 Background: Anti-PD-1/PD-L1 antibody has been approved as first- or second-line therapy in non-small cell lung cancer (NSCLC) patients and modified the management of patients with locally advanced or metastatic NSCLC. However, anti-PD-1 treatment shows less effective in patients with EGFR mutation than in those without driver gene mutation. To determine the activity of anti-PD-1 antibody in EGFR mutant NSCLC, we retrospectively evaluated response patterns among EGFR mutant NSCLC patients. Methods: We identified 58 patients with EGFR mutation who were treated with anti-PD-1 monotherapy or anti-PD-1 antibody combined with chemotherapy from March 2018 to December 2019. All of patients have received more than one treatment regimen including EGFR-TKI treatment. Objective response rates (ORR) were assessed using RECIST v1.1. Results: A total of 58 patients including 53 cases of lung adenocarcinoma, 4 cases of squamous cell carcinoma and 1 case of adenosquamous carcinoma were analyzed. Among them 26 patients received nivolumab treatment, 9 patients with pembrolizumab treatment, 9 patients with sintilimab treatment, 8 patients with JS001 treatment and 6 patients with camrelizumab treatment. Seven patients received anti-PD-1 monotherapy and the other 51 patients received anti-PD-1 combined chemotherapy. The main chemotherapeutic drugs contain docetaxel, pemetrexed, paclitaxel and paclitaxel-albumin. ORR was observed in 6 out of 58 (10%) patients. The disease control rate was 50% (29/58). The median PFS was 2.82 months. All six patients who achieved PR were received anti-PD-1 combined chemotherapy. Four patients died during treatment with anti-PD-1 therapy and we can’t confirm if these were due to cancer progress or immune related tumor hyperprogression. The adverse events were immune related pneumonia (two cases with grade 2 and one case with grade 3) and immune related hepatitis (one case with grade 2). Conclusions: Anti-PD-1 antibody combined chemotherapy seems showed moderate effect on NSCLC patients with EGFR mutation who have received anti-EGFR therapy.

Neratinib, an Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor: Results of a Phase II Trial in Patients With Advanced Non–Small-Cell Lung Cancer

2010 ◽  
Vol 28 (18) ◽  
pp. 3076-3083 ◽  
Author(s):  
Lecia V. Sequist ◽  
Benjamin Besse ◽  
Thomas J. Lynch ◽  
Vincent A. Miller ◽  
Kwok K. Wong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Objective Response ◽  
Resistance Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung

PurposeEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have had a significant impact on non–small-cell lung cancer (NSCLC) outcomes, particularly for patients with EGFR mutations. Resistance emerges after 9 to 12 months, primarily mediated by the T790M resistance mutation. We studied neratinib, an irreversible pan-ErbB TKI that may overcome T790M.Patients and MethodsPatients with advanced NSCLC underwent EGFR sequencing of available tumor tissue at enrollment. Those with ≥ 12 weeks of prior TKI therapy were placed in arm A if they were EGFR mutation positive or arm B if they were wild-type. Arm C included TKI-naïve patients with adenocarcinoma and light smoking histories (≤ 20 pack-years). All patients received daily oral neratinib, initially at 320 mg but subsequently reduced to 240 mg because of excessive diarrhea. The primary end point was objective response rate (RR).ResultsOne-hundred sixty-seven patients were treated: 91 in arm A, 48 in arm B, and 28 in arm C. Diarrhea was the most common toxicity; grade 3 incidence was 50% at 320 mg but improved to 25% after dose reduction. The RR was 3% in arm A and zero in arms B and C. No patients with known T790M responded. Notably, three of four patients with an exon 18 G719X EGFR mutation had a partial response and the fourth had stable disease lasting 40 weeks.ConclusionNeratinib had low activity in patients with prior benefit from TKIs and in TKI-naïve patients, potentially because of insufficient bioavailability from diarrhea-imposed dose limitation. Responses were seen in patients with the rare G719X EGFR mutation, highlighting the importance of obtaining comprehensive genetic information on trials of targeted agents.

scholarly journals Continued gefitinib retreatment beyond progression in patients with advanced non-small cell lung cancer harboring sensitive EGFR mutations

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052095503
Author(s):  
Xuhong Jiang ◽  
Xiaoqing Li ◽  
Lingli Tu ◽  
Jin Cai ◽  
Man Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung

Purpose To evaluate the effectiveness and safety of gefitinib retreatment beyond disease progression in patients with advanced non-small cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor ( EGFR) mutations. Methods Data from patients with stage III/IV NSCLC were analyzed retrospectively. Patients with sensitive EGFR mutations received first-line treatment with gefitinib followed by retreatment with gefitinib after disease progression. Progression-free survival (PFS) after the first treatment (PFS-1) was defined as the time to progression or death using the Response Evaluation Criteria in Solid Tumors criteria (RECIST) v1.1 criteria. The second PFS (PFS-2) was defined as the interval between the first and second progressions, at the investigator’s discretion. Toxicities were recorded in accordance with the National Cancer Institute (NCI)-Common Terminology Criteria (CTC) version 4.0. Results Sixteen patients aged 53 to 80 years (median 66 years) were included in the analysis. The median PFS-1 and PFS-2 were 10.0 months and 14.0 months, respectively. The median overall survival (OS) was 36.0 months. No toxicity of grade 3 or worse was observed. Conclusions Our findings suggest that gefitinib retreatment beyond disease progression may be an effective and tolerable approach for NSCLC patients with sensitive EGFR mutations.

Response to Osimertinib in a Patient With Non-Small Cell Lung Cancer and Two Uncommon EGFR mutations

2020 ◽  
pp. 10-13
Author(s):  
Christoforos Astaras ◽  
Adrienne Bettini ◽  
Daniel C. Betticher
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Genetic Alterations ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20

In advanced non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutations are one of the most frequent oncogenic drivers. They confer a favorable prognosis and strongly predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Over the last decades, several EGFR genetic alterations, common and uncommon mutations, have been described in exons 18−21. Common mutations are exon 19 deletions (most frequently E746-A750) and exon 21 L858R substitution. Uncommon mutations include exon 18 G719X, exon 20 S768l, exon 21 L861Q and many other rare ones. This report describes the case of a 55-year-old woman with a newly diagnosed metastatic lung adenocarcinoma harboring two rare EGFR mutations and showing sustained response to osimertinib.

scholarly journals Successful Treatment of Afatinib-Refractory Non-Small Cell Lung Cancer with Uncommon Complex EGFR Mutations Using Pembrolizumab: A Case Report

2019 ◽  
Vol 12 (2) ◽  
pp. 564-567
Author(s):  
Yuri Taniguchi ◽  
Momoko Yamamoto ◽  
Hiroaki Ikushima ◽  
Sayaka Ohara ◽  
Hideyuki Takeshima ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Stage ◽  
Nsclc Patient ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Rapid Progression ◽  
Small Cell Lung

Although there has been significant progress in immune-checkpoint inhibitor (ICI) treatment, it remains controversial whether they should be used in the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). We herein report the case of an NSCLC patient with uncommon complex EGFR mutations (G719S and L861Q) who was refractory to afatinib treatment but who showed a good response to pembrolizumab treatment. A 65-year-old female ex-smoker was diagnosed with right upper lobe NSCLC (clinical stage IVB; cT2bN3M1c). She had received afatinib for two months, but her disease showed rapid progression. Pembrolizumab treatment was initiated because more than 75% of her tumor cells expressed PD-L1. Her tumor responded well to pembrolizumab treatment and it remained effective for more than 1 year. Our case suggests that pembrolizumab treatment is a treatment option for NSCLC patients with uncommon EGFR mutations and high PD-L1 expression levels who are refractory to EGFR-TKI treatment.

Frequency and types of EGFR mutations in Moroccan patients with non–small cell lung cancer

2020 ◽  
pp. 030089162096457
Author(s):  
Mohamed Lemine Sow ◽  
Hind El Yacoubi ◽  
Badreddine Moukafih ◽  
Salif Balde ◽  
Gloria Akimana ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Smoking Status ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Asian Populations ◽  
Moroccan Patients

Background: Mutations in the epidermal growth factor receptor ( EGFR) gene are commonly observed in non-small cell lung cancer (NSCLC), particularly in adenocarcinoma histology. The frequency of EGFR mutations is ethnicity-dependent, with a higher proportion reported in Asian populations than Caucasian populations. There is a lack of data on these mutations in north Africa. Methods: Tumor specimens from Moroccan patients with NSCLC were collected from five pathology laboratories between November 2010 and December 2017 to determine frequency and types of EGFR mutations. Tumors were tested in a reference center for EGFR by polymerase chain reaction and sequencing of exons 18, 19, 20, and 21. Results: A total of 334 patients were enrolled: 242 (72.5%) males and 92 females (27.5%). A total of 56.9% had a history of smoking. EGFR testing of the 334 lung adenocarcinoma samples demonstrated a wild-type EGFR in 261 (78.1%) and mutated EGFR in 73 (21.9%). Mutations were mainly detected in the exon 19 deletion (65.8%), followed by exon 21 L858 (17.8%) and other exon 21 codon mutations (5.5%) and exon 18 (6.8%), whereas primary mutations of exon 20 were less frequent (4.1%). In patients with advanced NSCLC, the detection of EGFR mutation was independently associated with sex (41.3% female vs 14.5% male; p < 0.001) and smoking status (34.8% nonsmokers vs 12.9% active smokers; p < 0.001). The mean age was significantly different between the two groups ( p = 0.041). Conclusion: Our findings confirm the genetic heterogeneity of NSCLC worldwide, reporting frequency of EGFR mutations in Moroccan patients with NSCLC between those of Asian and Caucasian populations.

scholarly journals EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes

2019 ◽  
Vol 37 (4) ◽  
pp. 278-285 ◽  
Author(s):  
Nicolas Marcoux ◽  
Scott N. Gettinger ◽  
Grainne O’Kane ◽  
Kathryn C. Arbour ◽  
Joel W. Neal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Recurrent Mutations ◽  
Egfr Mutant ◽  
Neuroendocrine Carcinomas

Purpose Approximately 3% to 10% of EGFR (epidermal growth factor receptor) -mutant non–small cell lung cancers (NSCLCs) undergo transformation to small-cell lung cancer (SCLC), but their clinical course is poorly characterized. Methods We retrospectively identified patients with EGFR-mutant SCLC and other high-grade neuroendocrine carcinomas seen at our eight institutions. Demographics, disease features, and outcomes were analyzed. Results We included 67 patients—38 women and 29 men; EGFR mutations included exon 19 deletion (69%), L858R (25%), and other (6%). At the initial lung cancer diagnosis, 58 patients had NSCLC and nine had de novo SCLC or mixed histology. All but these nine patients received one or more EGFR tyrosine kinase inhibitor before SCLC transformation. Median time to transformation was 17.8 months (95% CI, 14.3 to 26.2 months). After transformation, both platinum-etoposide and taxanes yielded high response rates, but none of 17 patients who received immunotherapy experienced a response. Median overall survival since diagnosis was 31.5 months (95% CI, 24.8 to 41.3 months), whereas median survival since the time of SCLC transformation was 10.9 months (95% CI, 8.0 to 13.7 months). Fifty-nine patients had tissue genotyping at first evidence of SCLC. All maintained their founder EGFR mutation, and 15 of 19 with prior EGFR T790M positivity were T790 wild-type at transformation. Other recurrent mutations included TP53, Rb1, and PIK3CA. Re-emergence of NSCLC clones was identified in some cases. CNS metastases were frequent after transformation. Conclusion There is a growing appreciation that EGFR-mutant NSCLCs can undergo SCLC transformation. We demonstrate that this occurs at an average of 17.8 months after diagnosis and cases are often characterized by Rb1, TP53, and PIK3CA mutations. Responses to platinum-etoposide and taxanes are frequent, but checkpoint inhibitors yielded no responses. Additional investigation is needed to better elucidate optimal strategies for this group.

scholarly journals Experience from Asian centers in a named-patient-use program for afatinib in patients with advanced non-small-cell lung cancer who had progressed following prior therapies, including patients with uncommon EGFR mutations

2021 ◽  
Vol 26 (5) ◽  
pp. 841-850
Author(s):  
Gee-Chen Chang ◽  
David Chi-Leung Lam ◽  
Chun-Ming Tsai ◽  
Yuh-Min Chen ◽  
Jin-Yuan Shih ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Options ◽  
Objective Response ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Clinical Benefits ◽  
Patient Use

Abstract Background This study evaluated outcomes among patients with advanced/metastatic non-small-cell lung cancer (NSCLC) treated at Asian centers participating in the global named-patient-use (NPU) program for afatinib. Methods Patients had progressed after initial benefit with erlotinib or gefitinib, and/or had an EGFR or HER2 mutation, had no other treatment options, and were ineligible for afatinib trials. The recommended starting dose of afatinib was 50 mg/day. Dose modifications were allowed, and afatinib was continued as long as deemed beneficial. Response and survival information was provided voluntarily. Safety reporting was mandatory. Results 2242 patients (26% aged ≥ 70 years, 96% with adenocarcinoma) received afatinib at centers in 10 Asian countries. Most were heavily pre-treated, including prior treatment with erlotinib or gefitinib. Of 1281 patients tested, 1240 had EGFR mutations (common: 1034/1101; uncommon: 117/1101). There were no new safety signals, the most common adverse events being rash and diarrhea. Objective response rate (ORR) was 24% overall (n = 431 with data available), 27% for patients with common EGFR mutations (n = 230) and 28% for those with uncommon mutations (n = 32); median time to treatment failure (TTF) in these groups was 7.6 months (n = 1550), 6.4 months (n = 692) and 8.4 months (n = 83), respectively. In patients with EGFR exon 20 insertions (n = 23) and HER2 mutations (n = 12), median TTF exceeded 12 months. Conclusions Patient outcomes in this study were similar to those reported in the analysis of the global NPU. Afatinib achieved clinical benefits in patients with refractory NSCLC. ORR and TTF were similar between patients with tumors harboring uncommon and common EGFR mutations.

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