Lung Cancer Harboring EGFR Mutations Research Articles

Phase II Trial of Afatinib in Patients With EGFR-Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A.

National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) was a multicohort phase 2 trial that assigned patients with advanced pretreated cancers to molecularly targeted therapies on the basis of tumor genomic testing. NCI-MATCH Arm A evaluated afatinib, an EGFR tyrosine kinase inhibitor (TKI) approved for advanced non-small cell lung cancer, in patients with tumors other than lung cancer harboring EGFR mutations. Patients with advanced pretreated cancers other than lung cancer found to have selected actionable EGFR mutations were offered participation in Arm A. Previous therapy with an EGFR TKI was not allowed. Patients received afatinib 40 mg once daily continuously until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), 6-month PFS, and overall survival (OS). Seventeen patients received protocol therapy. Tumor types included glioblastoma multiforme (GBM) (13), gliosarcoma (1), adenocarcinoma not otherwise specified (NOS) (2), and adenosquamous carcinoma of the breast (1). Fifty-nine percent of patients received ≥2 lines of previous therapy. The ORR was 11.8% (90% CI, 2.1 to 32.6), with one complete response lasting 16.4 months (GBM harboring a rare exon 18 EGFR-SEPT14 fusion) and one partial response lasting 12.8 months (adenocarcinoma NOS with the classic EGFR mutation, p.Glu746_Ala750del). Three patients had stable disease. The 6-month PFS was 15% (90% CI, 0 to 30.7); the median OS was 9 months (90% CI, 4.6 to 14.0). Rash and diarrhea were the most common toxicities. Afatinib had modest activity in a cohort of patients with heavily pretreated cancer with advanced nonlung, EGFR-mutated tumors, but the trial's primary end point was not met. Further evaluation of afatinib in GBM with EGFR exon 18 fusions may be of interest.

Predictive value of co-existing genetic alterations and tumor mutation burden for patients with completely resected non-small cell lung cancer harboring EGFR mutation: Biomarker analysis of phase III IMPACT study.

8524 Background: Although osimertinib has recently become an option for adjuvant therapy in many countries, biomarkers predicting the efficacy of adjuvant EGFR-TKI and the risk of postoperative recurrence in completely resected NSCLC harboring EGFR mutations have not been fully investigated. Methods: This IMPACT-TR study is an exploratory biomarker study for completely resected, EGFR-mutated NSCLC patients who received gefitinib or cisplatin plus vinorelbine (cis/vin) in a phase III IMPACT study (Trial registration number: UMIN000044738. Funding: AstraZeneca K.K.). Surgically resected lung cancer tissue specimens were analyzed for co-existing somatic mutations and tumor mutation burden (TMB) determined by Oncomine Tumor Mutation Load, and these data were matched with disease free survival (DFS) and overall survival (OS) data. Results: Of the 234 patients in the IMPACT study, 211 patients were enrolled, and 202 patients in the Per Protocol Set were analyzed. The most frequent co-existing somatic mutation was TP53 (58.4%), followed by CSMD3 (11.8%), NOTCH1 (9.9%) and SYNE1 (9.9%). The median TMB was 6.67 mutations/Mb, and only 15.2% had ≥10 mutations/Mb. EGFR mutation subtypes, TP53 co-mutation and TMB were not associated with DFS or OS in either the gefitinib or cis/vin groups. In the gefitinib group, patients with NOTCH1 mutation had significantly shorter OS (hazard ratio [HR] 4.18, 95%CI 1.65-10.61, p=0.003) and tended to have shorter DFS (HR 1.44, 95%CI 0.62-3.37, p=0.399) than those without NOTCH1 mutation. In the cis/vin group, patients with CREBBP mutation had significantly shorter DFS (HR 2.70, 95%CI 1.05-6.97, p=0.040) and tended to have shorter OS (HR 3.05, 95%CI 0.90-10.37, p=0.074) than those without CREBBP mutation. Conclusions: This study suggested that NOTCH1 mutation may be a biomarker to predict poor response to adjuvant gefitinib and CREBBP mutation to predict poor response to cis/vin in patients with completely resected, EGFR-mutated NSCLC. Clinical trial information: UMIN000044738 .

982P Final results and biomarker analysis of a randomized phase II study of osimertinib plus bevacizumab versus osimertinib monotherapy for untreated patients with non-squamous non-small cell lung cancer harboring EGFR mutations: WJOG9717L study

Previous studies showed that the addition of anti-VEGF inhibitors to erlotinib prolonged progression-free survival (PFS) in EGFR mutated non-squamous non-small-cell lung cancer (Ns-NSCLC) patients (pts). The primary results of WJOG9717L study, open-label, randomized phase II trial comparing Osimertinib (Osi) plus bevacizumab (Bev) with Osi monotherapy for untreated pts with advanced EGFR mutated Ns-NSCLC, were reported at ESMO2021.

Real-World Patient Characteristics, Treatment Patterns, and Mutation Testing Patterns Among US Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR Mutations.

Approximately 15% of patients with non-small cell lung cancer (NSCLC) harbor an epidermal growth factor receptor mutation (EGFRm). Mutation testing (including EGFRm) is recommended for patients with advanced NSCLC (aNSCLC) prior to initiating first-line therapy (L1) or after progression on targeted therapy. To elucidate current and future unmet needs, the present study characterized real-world EGFR testing patterns and treatment patterns in patients with aNSCLC. This retrospective observational cohort study evaluated newly diagnosed adult patients with aNSCLC (stageIIIB or higher) from the Flatiron Health database. Eligible patients received at least L1 during 2015-2020 (testing cohorts) or 2011-2020 (treatment cohorts). Eligible patients for the treatment cohorts had an EGFR mutation. The testing cohort included 22,726 patients, 75.5% had at least one EGFR test and 15.2% of those tested were positive for EGFR mutation. From 2015 to 2020, the median time from sample collection to test results decreased substantially while the proportion of NGS EGFR tests and use of plasma samples increased. The treatment cohort included 3701 patients (95% common mutations [cEGFR], 5.0% exon20 insertions [ex20ins]). Three or more lines of therapy (LOTs) were observed in approximately 30% of patients. For L1, most cEGFR patients received EGFR tyrosine kinase inhibitors (EGFR-TKI, 68.1%) or platinum-based chemotherapy (PBC, 24.8%); most ex20ins patients received PBC (66.1%) or EGFR-TKI (17.5%). The most common L2 was EGFR-TKI (54.1%) or PBC (22.8%) for cEGFR and immunotherapy (25.9%) or PBC (25.9%) for ex20ins. No predominant L3 was evident in either group. This real-world study, among the largest analyses of testing patterns for patients with aNSCLC, demonstrates a comprehensive view of treatment patterns for patients with EGFR mutations, including ex20ins. Despite recent improvement, increased use of EGFR testing, including advanced methods, is needed to optimize treatment pathways and outcomes. Additionally, the lack of a predominant therapy in later lines indicates a need for new therapies.

P48.06 A Network Meta-Analysis (MA) of First-Line Lung Cancer Treatment With Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs)

Over the last two decades, the treatment options for non-small cell lung cancer harbouring EGFR mutations have expanded rapidly from chemotherapy to encompass first, second and third generation TKIs alone or as part of combination therapy. While chemotherapy, gefinitib and erlotinib have often been used as comparator arms in clinical trials, newer standard options like osimertinib, afatinib, dacomitinib and combination therapies have rarely been compared directly for efficacy or toxicity outcomes.

1242P Anlotinib with gefitinib as first-line therapy in advanced non-small cell lung cancer harboring EGFR mutations: A phase II study

Anti-angiogenic monoclonal antibodies combined with EGFR-TKI has shown excellent efficacy and prolong PFS in patients(pts) with EGFR mutations. Anlotinib, an oral and multi-target tyrosine kinase inhibitor, has significantly improved OS and PFS in advanced NSCLC pts in the ALTER0303 study. This is the first trial evaluating anlotinib plus gefitinib in treatment-naive advanced NSCLC pts.

LBA44 Primary results of a randomized phase II study of osimertinib plus bevacizumab versus osimertinib monotherapy for untreated patients with non-squamous non-small cell lung cancer harboring EGFR mutations: WJOG9717L study

Osimertinib (Osi) has been a standard treatment for untreated patients (pts) with non-small-cell lung cancer (NSCLC) harboring an EGFR mutation. Previous studies showed that the addition of anti-VEGF inhibitors to erlotinib prolonged progression-free survival (PFS) in EGFR mutated non-squamous NSCLC (Ns-NSCLC) pts. This phase II, open-label, randomized trial was conducted to compare Osi plus bevacizumab (Bev) with Osi monotherapy for untreated pts with advanced EGFR mutated Ns-NSCLC.

An open-label expanded access program of afatinib in EGFR tyrosine kinase inhibitor-na\xefve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations

BackgroundAfatinib is approved globally for EGFR-TKI treatment-naïve patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). In this Korean expanded access program, we evaluated its ‘real-world’ safety and efficacy.MethodsEGFR-TKI treatment-naïve patients with EGFR mutation-positive NSCLC received afatinib 40 mg/day until disease progression or other withdrawal criteria. Dose reductions were permitted for adverse events (AEs). The primary endpoint was the number of patients with AEs (CTCAE version 3.0). Other endpoints included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and changes in investigator-assessed cancer-related symptoms.ResultsEighty-eight patients received afatinib, including 27 (31%) with brain metastases and 16 (18%) with uncommon EGFR mutations. Median PFS was 17.0 months (95% confidence interval [CI] 12.9–23.3 months). Grade 3 treatment-related AEs (TRAEs) were reported in 51 (58%) patients; the most common were diarrhea (22%) and rash/acne (20%). No grade > 3 TRAEs were reported. AEs leading to dose reduction occurred in 49 (56%) patients. Treatment discontinuation due to TRAEs occurred in 4 (5%) patients. ORR was 81% overall, 89% in patients with brain metastases, and 55% in patients with uncommon mutations (excluding T790M/exon 20 insertions). Median DOR was 15.1 months (95% CI 12.4–21.4 months). Cancer-related symptoms were improved/unchanged/worsened in 34–66%/36–66%/0–3% of patients over the first year.ConclusionsNo unexpected safety signals for afatinib were observed. AEs were manageable; the treatment discontinuation rate was low. Afatinib showed encouraging efficacy in a broad patient population including those with brain metastases or tumors harboring uncommon EGFR mutations.Trials registrationClinicalTrials.gov NCT01931306; 29/08/2013.

Abstract 403: The landscape of PD-L1 expression in lung cancer harboring EGFR mutations

Abstract Background: Results from previous studies indicated that lung cancer patients harboring EGFR sensitizing mutations may receive unfavorable outcomes from immunotherapy. The present study aims to investigate the landscape of PD-L1 expression in lung cancer harboring EGFR mutations. Methods: Tissue samples were subjected to NGS in a College of American Pathologists-certified and Clinical Laboratory Improvement Amendments-accredited lab for driver oncogene mutations and PD-L1 expression. Results: A total of 22143 lung cancer patients were selected, including 12278 (55.4%) male and 9865 (44.6%) female with a median age of 63. There are 9560 patients has the EGFR mutation, and the frequency of EGFR mutation is 43.2%. Among the EGFR mutation patients, 1602 patients have been collected tumor tissue, and the PD-L1 expression have been tested by FDA-approved SP263 and 22C3 antibodies. Among all the EGFR mutation cases assessed PD-L1 expression (n=1602), low PD-L1 expression levels (<1%) were more than half proportion with 56.5% (n=905), PD-L1 expression level of 1%-49% accounted for 31.2% (n=905), PD-L1 expression level of 50%-79% accounted for 9.1% (n=146), PD-L1 expression level of 80%-89% accounted for 1.8% (n=29), and PD-L1 expression level higher than 90% accounted for 1.4% (n=22). Conclusion: Our study supported that NSCLC patients harboring sensitizing oncogenic mutations may potentially benefit from anti-PD-1/L1 especially for those with positive indicators of immunotherapy with strong positive PD-L1 expression. Citation Format: Linlin Zhang, Fuyu Gong, Fanlu Meng, Xin Wang, DianSheng Zhong. The landscape of PD-L1 expression in lung cancer harboring EGFR mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 403.

Upfront thoracic radiotherapy to primary lession improve outcomes in patients with stage IV non-small cell lung cancer harboring EGFR mutations.

e21167 Background: The role of thoracic radiotherapy in the treatment of metastatic EGFR mutant non-small cell lung cancer patients in literature datas are insufficient.The aim of this study was to examine the effectiveness of upfront thoracic radiotherapy in metastatic EGFR mutant NSCLC patients treated with chemotherapy or TKI. Methods: This study was designed as a hospital-based retrospective observational case-series study. A total of 141 patients with metastatic EGFR mutant non-small cell lung cancer who has followed in two different oncology centers at Turkey between 2014 and 2020. have been included to this study. Results: The median age of the patients was 63 (range 35-91) years. EGFR mutation results of exon 19 deletion, exon 21 mutation and exon 18 mutation were found in 82 (58.2%), 56 (39.7%) and 3 (2.1%) patients, respectively. The median follow-up time was 22 months and 94 (33.3%) patients died during follow-up. Median overall survival (OS) was 26 months and progression free survival (for first line treatment) (PFS) was 10 months for whole patients, respectively. Radiotherapy was given to the primary tumor site in 32 (22,6%) patients. Patients receiving radiotherapy to primary tumor site had better overall survival than those not (31 versus 23 months respectively and p = 0,02) The survival advantage was also seen for patients group taking TKI at upfront setting (33 versus 23 months respectively and p = 0.05). Conclusions: In this study, we have showed that upfront thoracic radiotherapy to primary lession as combination with EGFR-TKI treatment may improve the outcome in advanced stage IV NSCLC patients harboring EGFR mutations.

P76.75 Clinical Outcome and Toxicity Profiles of Patients with EGFR-mutation Positive Non-Small-Cell Lung Cancer

Activating mutations of EGFR in advanced lung adenocarcinoma and its inhibition with specific tyrosine kinase inhibitors has been shown to generate clinically significant tumor responses. Treatment outcomes of advanced EGFR mutant lung carcinoma in Pakistani population are not previously reported. We conducted a study using the Real World Data (RWD) in patients with EGFR mutant advanced lung cancer treated at our institution. We evaluated clinical features, toxicity profile and outcome of these patients and compared it with those who were unable to receive TKI due to resource limitations. We identified 27 patients with advanced lung cancer harboring EGFR mutations that were treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from January 2013 till April 2020. EGFR mutation detection was achieved by real time PCR. Data were collected through electronic medical record. Five patients were excluded from the analysis as they did not start treatment and were lost to follow-up. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier curves and log-rank analysis. Of the 22 patients analyzed, 54.5% were males and 45.5% were females. Twenty patients (90.9%) presented with de novo stage IV disease. Age ranged from 34-84 years. Frequency of Exon 19 deletion, Exon 21 L858R mutation, Exon18G7196 mutation and Exon 20 mutation was 50%, 32%, 9% and 4.5% respectively. One patient had compound Exon18G719X and Exon20S7681 mutation. 18.2% of patients had CNS metastasis at initial presentation. We identified 4 groups in our patient population. Group-1 consisted of patients who received first-generation TKI followed by third-generation TKI upon progression. Group-2 consisted of patients who received upfront first-generation TKI followed by chemotherapy upon progression. Group-3 consisted of patients who received upfront chemotherapy followed by a first-generation TKI upon progression and Group-4 consisted of patients who received upfront chemotherapy followed by second-line chemotherapy upon progression. These groups reflect the real world issues of TKI affordability in a Low Middle Income country (LMIC) such as Pakistan. Median PFS on first-line treatment (PFS1) was 10.7 months in the upfront chemotherapy group, versus 14.5 months in the upfront TKI group (p-value = 0.280). Median PFS on second-line treatment (PFS2) was 4.4 months in the chemotherapy group versus 23.7 months in the TKI group (p-value = 0.001). Median OS in Group 2, 3 and 4 was 20.0, 85.6 and 26.0 months respectively and not yet reached in Group 1 (p = 0.271). 27.8% patients developed grade I-II skin rash and diarrhea, 5.6% developed grade III-IV anemia, grade I-II neutropenia, and grade III-IV hyperbilirubinemia Within the constraints of a small sample size our real world data shows that the use of EGFR TKI in advanced EGFR mutant lung cancer is well tolerated in a Pakistani population. Use of EGFR TKI yields a superior PFS in both upfront and subsequent line of therapy which is consistent with the previously reported data. Preliminary overall survival favors superior outcome in the TKI group compared to chemotherapy alone or chemo-TKI combination groups.

P76.10 Erlotinib Plus Anlotinib as First-Line Therapy in Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: An Open-Label, Phase 2 Study

P76.10 Erlotinib Plus Anlotinib as First-Line Therapy in Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: An Open-Label, Phase 2 Study

Treatment strategy optimization for patients with non-small-cell lung cancer harboring EGFR mutation: a Delphi consensus

AimTo stablish a consensus on the treatment strategy for advanced non–small-cell lung cancer (aNSCLC) with epidermal growth factor receptor mutation (EGFRm) in Spain.MethodsAfter a systematic literature review, the scientific committee developed 33 statements in 4 fields: molecular diagnosis (10 items); histologic profile and patient clinical characteristics (7 items); first-line (1L) treatment in EGFRm aNSCLC (8 items); and subsequent-line treatment (8 items). A panel of 31 experts completed 2 Delphi online questionnaires rating their degree of agreement/disagreement for each statement through a 1–9 range scale (1–3 = disagree, 7–9 = agree). Consensus was reached if 2/3 of the participants are in the median range.ResultsIn the first Delphi round consensus was achieved for 24/33 of the statements. One of the assertions was deleted, proceeding to a second round with the eight remaining questions with no consensus or in the range of indeterminacy. Determination of the EGFR status from tissue and analysis of the different biomarkers are two important variables that influenced treatment decision in patients with aNSCLC. 1L treatment should be the best therapeutic option, independently of the subsequent lines of treatment. For patients with the most common activating mutations osimertinib was considered the most efficient and safe 1L option. In case of disease progression, a new biopsy was needed.ConclusionsA consensus document is proposed to optimize the treatment strategy for untreated patients with a NSCLC with EGFR sensitizing mutations.

408P Integrated chemotherapy with EGFR receptor tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring EGFR mutation

408P Integrated chemotherapy with EGFR receptor tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring EGFR mutation

Beneficial effect of erlotinib and trastuzumab emtansine combination in lung tumors harboring EGFR mutations

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is the standard therapy for non-small cell lung cancer (NSCLC) harboring EGFR mutations, but the resistance is inevitable. The drug-tolerant persister cancer cells are thought to be involved in the resistance. We recently reported that HER2 expression had a negative impact on time-to-treatment-failure in patients with EGFR mutant NSCLC. In this study, we hypothesized that HER2 might be a potential target for alternative combination therapy in NSCLC harboring EGFR mutations. In vitro study showed that the level of HER2 expression had no correlation with the sensitivity to EGFR-TKI, erlotinib but showed some correlation with HER2-inhibitor, ado-trastuzumab emtansine (T-DM1) in multiple EGFR-mutant lung cancer cell lines. In addition, HER2 expression was increased in persister cancer cells in 11–18 cell line harboring EGFR L858R or HCC827 cell line harboring EGFR exon 19 deletion after the exposure to erlotinib in vitro and in vivo. The combination of erlotinib and T-DM1 showed a superior inhibitory effect on cell proliferation compared with those of the erlotinib or T-DM1 alone in either 11–18 or HCC827 cells in vitro. The combination therapy also induced a significantly greater inhibitory effect on tumor growth in xenograft model in mice transplanted with either 11–18 or HCC827 cells compared with erlotinib alone or T-DM1 alone. No body weight loss was observed in these mice. These results suggested that the combination therapy with EGFR-TKI and T-DM1 might be a potentially promising strategy for treating lung cancer harboring EGFR mutations.

A phase II study of osimertinib for patients with radiotherapy-naïve CNS metastasis of non-small cell lung cancer harboring EGFR mutations: The OCEAN study (LOGIK 1603/WJOG 9116L).

9597 Background: Approximately 15%–30% of patients treated with EGFR-TKIs experience central nervous system (CNS) progression. Although radiotherapy is a standard treatment for CNS metastasis, the efficacy of radiotherapy against CNS is poor. The aim of OCEAN study was to assess the efficacy of osimertinib for patients with radiotherapy-naïve CNS metastasis of NSCLC harboring EGFR mutations. Methods: OCEAN study was two-cohort phase II trial, 65 patients (T790M cohort; 40 patients and first-line cohort; 25 patients) with radiotherapy-naïve CNS metastasis of EGFR mutation-positive NSCLC was included. Patients were treated with osimertinib 80 mg once daily. The primary endpoint was the response rate of brain metastasis (BMRR) assessed by the PAREXEL criteria. We set a threshold value of 50% and an expected value of 70% based on the overall response rate (ORR) of AURA trial. Based on one-sided alpha = 0.05 and power = 0.8, the sample size of T790M cohort was calculated to be 40. Key secondary endpoints were progression-free survival (PFS), and ORR, BMRR assessed by the RECIST criteria. We are exploratorily assessing the blood concentration of osimertinib at day 22, which considered to represent steady state. In this report, we present the results of T790M cohort. Results: Between October 2016 to July 2019, 40 participants were recruited in the T790M cohort. The median age was 66.5 with 30.0% male. Eight patients had symptomatic CNS metastasis and most patient had multiple CNS metastasis (77.5%). BMRR assessed by PAREXEL criteria was 66.7% (95%CI: 54.3 – 79.1%) and BMRR assessed by RECIST was 70.0% (95%CI, 49.9 – 90.1%). Median PFS was 7.1 months (95%CI, 3.4 – 13.6 months) and ORR assessed by RECIST was 40.5% (95%CI, 24.7 – 57.9%). Treatment related pneumonitis was observed in 4 patients (10.0%). There was no grade 3 or higher toxicities that were found in more than 10%. Conclusions: This first study assessed the efficacy of osimertinib for patients with radiotherapy-naïve CNS metastasis of EGFR T790M mutation-positive NSCLC. The OCEAN study met primary endpoint. The results of this study suggested that patients with brain metastasis harboring EGFR T790M mutations had better to receive osimertinib prior to brain radiotherapy. Clinical trial information: 071180017 .

Comparisons of outcomes between first and second generations EGFR-TKIs in stage IV non-small cell lung cancer harboring EGFR mutations

Introduction L’objectif de cette etude retrospective etait de comparer la survie et la tolerance des inhibiteurs de tyrosine kinase (ITK) de premiere et de seconde generation chez des patients atteints d’adenocarcinomes bronchiques metastatiques mutes EGFR non selectionnes rencontres en pratique courante. Methodes Dans cette etude multicentrique, les donnees de tous les patients atteints d’adenocarcinome de stade IV mute EGFR et traites par ITK (1re ou 2e generation) entre 2010 et 2018 ont ete revues. Les patients ont ete assignes en 2 groupes : ITK de 1re generation (erlotinib et gefitinib) vs ITK de 2e generation (afatinib). La survie a ete evaluee a l’aide d’un test du Log-rank et du modele a risque proportionnel de Cox. Resultats Deux cent soixante-huit patients ont ete inclus dont 221 (82,5 %) traites par ITK de 1re generation et 47 (17,5 %) par afatinib. Dans les 2 groupes, l’âge median des patients etait similaire (68,40 ans [IQR : 8,28] vs 68,43 ans [IQR : 6,54], p = 0,89), de meme que la proportion de femmes (82,4 % vs 87,2 %, p = 0,42). Les patients du groupe afatinib etaient plus alteres sur le plan general (PS ≥ 2 : 21,3 % vs 13,6 %, p = 0,004), avaient une maladie plus avancee (stade M1b ou M1c : 80,9 % vs 63,3 %, p = 0,004) avec plus de metastases cerebrales, et etaient porteurs de mutations plus rares (25,5 % vs 5,5 %, p Conclusion Dans cette etude, il n’a pas ete mis en evidence de benefice de l’afatinib, comparativement aux ITK de 1re generation en termes de survie chez les patients fragiles.

A Retrospective Analysis of the Factors Affecting the Detection of T790M-resistant Mutation on Rebiopsies for Patients with Non-small-cell Lung Cancer Harboring EGFR Mutations

A Retrospective Analysis of the Factors Affecting the Detection of T790M-resistant Mutation on Rebiopsies for Patients with Non-small-cell Lung Cancer Harboring EGFR Mutations

Negative impact of malignant effusion on osimertinib treatment for non-small cell lung cancer harboring EGFR mutation

Summary3rd-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, have reasonable efficacy in non–small-cell lung cancers (NSCLC) with EGFR mutations. However, the efficacy of osimertinib in NSCLC patients with fluids, such as pleural, pericardial and abdominal effusions, is unclear. We evaluated the efficacy of osimertinib in this specific setting. NSCLC patients harboring EGFR T790 M mutations who experienced progressive disease after first EGFR-TKI treatment and started osimertinib treatment between April 2016 and August 2018 were retrospectively screened. In particular, we assessed the efficacy of osimertinib for NSCLC with EGFR T790 M mutations in patients who were diagnosed with EGFR T790 M mutation by malignant effusion. Among 90 patients with EGFR T790 M mutation who started osimertinib treatment after EGFR-TKI failure, 21 were diagnosed from malignant effusions excluding cerebrospinal fluid (F group) and 69 using other methods including tissue biopsies (NF group). Patient characteristics were well-balanced between the two groups. Overall response was 50%, and significantly worse in the F group (29%) than the NF group (57%; P = 0.025). Median progression-free survival with osimertinib treatment in the F group (7.1 months, 95% confidence interval [CI]: 2.3–14.0) was significantly shorter than that in the NF group (11.9 months, 95% CI: 9.5–16.0; P = 0.046)). Median drainage-free time was 10.9 months (95% CI: 1.4 months– not reached). The present study showed that the efficacy of osimertinib for NSCLC in which EGFR T790 M mutation is detected by malignant effusion may be less than in EGFR T790 M-mutated NSCLC detected by other methods.

The impact of the tumor shrinkage by initial EGFR inhibitors according to the detection of EGFR-T790M mutation in patients with non-small cell lung cancer harboring EGFR mutations

BackgroundThe EGFR-T790M mutation is clinically detected using re-biopsy in approximately 50% of patients with acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC) who harbor EGFR mutations. However, little is known about the population of NSCLC patients who develop acquired resistance due to the T790M mutation. In this study, we focused on the emergence of the T790M mutation and analyzed patients refractory to initial EGFR-TKIs with successful re-biopsy samples.MethodsSeventy-eight advanced NSCLC patients with EGFR mutations who had successful re-biopsy samples after resistance to initial EGFR-TKI treatment were enrolled at 5 institutions in Japan. We validated the association between the emergence of the T790M mutation and their clinical profiles.ResultsThirty-nine patients tested positive for T790M and 39 tested negative in the re-biopsy samples. The objective response rate to initial EGFR-TKIs was higher in patients with the T790M mutation than in those without the mutation (89.7% versus 51.2%, p < 0.001). Moreover, there was a significant difference in the maximal tumor shrinkage rate relative to baseline in T790M-positive tumors compared with T790M-negative tumors (42.7% versus 24.0%, p = 0.001). Multivariate analysis demonstrated that the maximum tumor shrinkage rate was a significant predictive factor for the detection of the T790M mutation (p = 0.023, odds ratio 1.03, 95% confidence interval 1.00–1.05).ConclusionsOur retrospective observations suggested that the maximum tumor shrinkage rate with initial EGFR-TKI treatment might be one of the promising predictive biomarkers for emerging refractory tumors with the EGFR-T790M mutation.