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T. Kato
Moderator of
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OA10 - EGFR Mutations (ID 382)
- Event: WCLC 2016
- Type: Oral Session
- Track: Biology/Pathology
- Presentations: 8
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OA10.01 - Comprehensive Genomic Profiling and PDX Modeling of EGFR Exon 20 Insertions: Evidence for Osimertinib Based Dual EGFR Blockade (ID 4375)
11:00 - 11:10 | Author(s): J.W. Riess, D.R. Gandara, G.M. Frampton, M. Cheng, P. Lara, K. Kelly, C. Ye, R. Madison, N. Peled, J.A. Bufill, G. Dy, S. Ou, D. Cross, C.J. Bult, S.D. Airhart, P.J. Stephens, J. Ross, V. Miller, S. Ali, J. Keck, P. Mack, A.B. Schrock
- Abstract
Background:
EGFR exon 20 insertion mutations (EGFRex20ins) comprise a subset of EGFR activating alterations relatively insensitive to 1[st] and 2[nd] generation EGFR-TKIs. Comprehensive genomic profiling (CGP) integrated with PDX modeling may identify new EGFR-inhibition strategies for EGFRex20ins.
Methods:
EGFRex20ins and co-occurring genomic alterations were identified by hybrid-capture based CGP performed on 14,483 consecutive FFPE lung cancer specimens to a mean coverage depth of >650X for 236 or 315 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. An EGFRex20ins(N771_P772>SVDNP)/EGFR-amplified tumor (24 copies) from this cohort was implanted subcutaneously into the flank of NOD.Cg-Prkdc[scid]Il2rg[tm1Wjl]/SzJ (NSG) mice for tumor growth inhibition studies (TGI) with vehicle, erlotinib (50 mg/kg PO daily), osimertinib (25 mg/kg PO daily), and osimertinib (25 mg/kg PO daily) plus cetuximab (10 mg/kg IV, 2x/week) administered for 21 days.
Results:
CGP identified 263/14,483 cases (1.8%) with EGFRex20ins, which represent 12% (263/2,251) of EGFR activating mutations in this series. 90% (237/263) were NSCLC-adenocarcinoma, 9% (23/263) were NSCLC-NOS, and 1% (2/263) were sarcomatoid carcinoma. Over 60 unique EGFRex20ins were identified, most commonly D770_N771>ASVDN (21%) and N771_P772>SVDNP (20%); 6% (15/263) harbored EGFR A763_Y764insFQEA, an EGFRex20ins typically sensitive to erlotinib. Among EGFRex20ins cases, EGFR-amplification occurred in 22% (57/263). Putative co-occurring driver alterations including EGFR (ex19del and L858R), Her2, MET and KRAS tended to be mutually exclusive, occurring only in 5% (12/263) of cases. The most common co-occurring alterations affected TP53 (56%), CDKN2A (22%), CDKN2B (16%), NKX2-1 (14%) and RB1 (11%). Average tumor mutation burden was low (mean 4.3 mutations/Mb, range 0-40.3 mutations/Mb). Clinical outcomes to 1st and 2nd generation EGFR-TKIs were obtained for a subset of cases with various EGFRex20ins, and 0/6 patients had responses. However, robust TGI was observed with combination osimertinib and cetuximab in a highly EGFR-amplified PDX model with a conserved EGFRex20ins (N771_P772>SVDNP) not associated with response to earlier generation EGFR-TKI, and was superior to vehicle, erlotinib or osimertinib alone (D21 mean tumor size 70 mm[3] vs. 1000, 800, 225 mm[3] respectively; p-values all <0.001).
Conclusion:
Diverse EGFRex20ins were detected in 12% of EGFR-mut NSCLC. Available clinical outcomes data demonstrated lack of response to 1[st] and 2[nd] generation EGFR-TKIs. Identification of co-occurring EGFR-amplification in 22% of cases led to testing of a dual EGFR blockade strategy with an EGFR monoclonal antibody and osimertinib, which demonstrated exceptional tumor growth inhibition in an EGFRex20ins PDX minimally responsive to erlotinib. These findings can rapidly be translated into an ongoing clinical trial of osimertinib and necitumumab.
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OA10.02 - Association of Variations in HLA-Class II and Other Loci with Susceptibility to EGFR-Mutated Lung Adenocarcinoma (ID 4192)
11:10 - 11:20 | Author(s): K. Shiraishi, Y. Okada, A. Takahashi, Y. Kamatani, K. Ashikawa, Y. Momozawa, H. Kunitoh, S. Matsumoto, A. Takano, K. Shimizu, A. Goto, K. Tsuta, S. Watanabe, Y. Ohe, Y. Watanabe, Y. Goto, H. Nokihara, K. Furuta, A. Yoshida, K. Goto, T. Hishida, M. Tsuboi, K. Tsuchihara, Y. Miyagi, H. Nakamura, T. Yokose, K. Tanaka, T. Nagashima, Y. Ohtaki, D. Maeda, K. Imai, Y. Minamiya, Y. Shimada, K. Sunami, M. Saito, J. Yokota, F. Matsuda, K. Matsuo, Y. Daigo, M. Kubo, T. Kohno
- Abstract
- Presentation
Background:
Lung adenocarcinoma (LADC) driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Understanding the genetic factors underlying such LADC is required to elucidate disease etiology and to identify effective methods of prevention.
Methods:
We investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls.
Results:
Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2, HLA-class II), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA-class II at 6p21.32 and 6p21.1 (FOXP4) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma (Shiraishi et al., Nature Communications, 2016, in press).
Conclusion:
This study indicates that multiple genetic factors, including an immunologic one, underlie the risk of lung adenocarcinomas with EGFR mutations.
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OA10.03 - YAP-NOTCH and STAT3 Signaling Rebound as a Compensatory Response to Gefitinib or Osimertinib Treatment in EGFR Mutant Lung Cancer (ID 4144)
11:20 - 11:30 | Author(s): R. Rosell, I. Chaib, N. Karachaliou, P. Cao, M.A. Molina Vila, X. Cai, A. Drozdowskyj, J. Yang, C. Hu, A.F. Cardona, A. Frías, C. Lazzari, A. Verlicchi, J. Codony Servat, C. Codony Servat, J.L. Ramírez Serrano, A. Vergnenegre, P.C. Ma, T. Bivona
- Abstract
- Presentation
Background:
Preclinical studies provide insights to therapy mechanisms of resistance that are not feasible with clinical studies. We investigated the signaling pathways that could be involved in adaptive resistance to gefitinib and/or osimertinib in EGFR mutant cells.
Methods:
We performed several laboratory methods to examine the signaling pathways involved in EGFR mutations. Signal transduction pathway analysis was designed using the Ingenuity Pathway Analysis (IPA) software (https://www.ingenuity.com/) Figure 1
Results:
Pathways mediating EGFR mutations are: i) ERK1/2 via Ras and MEK1/2 ii) AKT via PI3K and iii) STAT3 via JAK (Figure). By Western blot analysis, phosphorylation of Tyr705 on STAT3 was noted after 2 hours of gefitinib or osimertinib treatment in PC9 and H1975 EGFR mutant cells. Unexpectedly, YAP1 phosphorylation on Tyr357 and Notch activation was detected. Co-targeting STAT3 and Src with gefitinib or osimertinib ablates activation of STAT3 and YAP1-NOTCH3 signaling pathways (Figure). In vitro and in vivo, the combinatory therapy of gefitinib or osimertinib plus TPCA-1 (a dual inhibitor of IKKs and STAT3) plus saracatinib (a SFK inhibitor) leads to significant tumor shrinkage in PC9 and H1975 cells. In tumor samples of 64 EGFR mutant NSCLC patients treated with gefitinib, the median progression free survival (PFS) was significantly shorter in those with high levels of HES1, ALDH1A1, ALDH1A3, Bmi1, AXL, CDCP1, SHP2 and ILK (Figure). However, the mRNA levels of STAT3 and YAP1 stand out in the prediction of shorter PFS with a hazard ratio of 3.02 and 2.57, respectively (P<0.001)
Conclusion:
For the first time ever, we reported gefitinib induced activation of theYAP1-NOTCH signaling pathway, in addition to activation of STAT3, in EGFR mutant cells. Secondly, co-targeting STAT3 and Src, together with EGFR, causes significant tumor growth inhibition, in comparison with gefitinib or osimertinib single therapy.
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OA10.04 - Discussant for OA10.01, OA10.02, OA10.03 (ID 7008)
11:30 - 11:45 | Author(s): H. Borghaei
- Abstract
- Presentation
Abstract not provided
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OA10.05 - EGFR Gene Mutations Affect Tumor-Infiltrating Stromal Cell Components in Early-Stage Lung Adenocarcinoma (ID 6305)
11:45 - 11:55 | Author(s): T. Shima, T. Shigenobu, M. Shimoda, T. Ohtsuka, H. Asamura, Y. Kanai
- Abstract
- Presentation
Background:
Tumors are complex structures consisting of cancer cells surrounded by a tumor stroma that is now recognized to be critical for cancer progression. Although epidermal growth factor receptor (EGFR) mutations are frequently observed in non-small cell lung carcinoma, it remains poorly understood whether EGFR mutations in cancer cells affect the tumor stroma. In this study, we studied the status of EGFR mutations in early-stage lung adenocarcinoma and analyzed the relations of EGFR mutations to tumor-infiltrating stromal cell components.
Methods:
A total of 152 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete tumor resection in Keio University Hospital between 2010 and 2014 were studied. Genomic DNA was isolated from formalin-fixed, paraffin-embedded tumor sections and mutational analyses of EGFR gene exons 19, 20 and 21 were performed by a polymerase chain reaction-based method. Paraffin sections were also subjected to immunohistochemistry for CD3, FOXP3, CD163 or CD204. Numbers of CD3-, FOXP3-, CD163- or CD204-immunostained cells were counted by observing 5 different fields at x200 magnification.
Results:
EGFR mutations were detected in 71 (47%) of the 152 patients with clinical stage IA lung adenocarcinoma and were found more frequently in women and non-smokers. These contained 38 patients with missense mutations in exon 21 (L858R) and 30 patients with deletions in exon 19. By immunohistochemistry, the number of stromal macrophages positive for CD163 or CD204, markers for tumor-associated macrophages (TAMs), was significantly decreased within tumors with EGFR mutations compared to within those with wild-type EGFR, whereas the number of CD3[+] T cells or FOXP3[+] regulatory T cells was comparable between these groups. Both tumors with missense mutations in exon 21 and deletions in exon 19 had a similar trend toward decreased TAMs in the tumor stroma.
Conclusion:
Our data suggest that EGFR mutations in early-stage lung adenocarcinoma are associated with decreased TAMs in the tumor stroma. EGFR mutation status might act on not only cancer cell behavior but tumor microenvironment.
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OA10.06 - Characteristics and Outcomes of Patients with Lung Cancer Harboring Multiple Molecular Alterations (Biomarker IFCT Study) (ID 5425)
11:55 - 12:05 | Author(s): N. Guibert, F. Barlesi, R. Descourt, H. Léna, B. Besse, M. Beau-Faller, J. Mosser, E. Pichon, J. Merlio, L. Ouafik, F. Guichard, B. Mastroianni, L. Moreau, A. Wdowik, J. Sabourin, A. Lemoine, P. Missy, A. Langlais, D. Moro-Sibilot, J. Mazieres
- Abstract
- Presentation
Background:
Carcinogenesis of non-small cell lung cancer (NSCLC) can be driven by oncogenic addiction that can be targeted by specific inhibitors. It is commonly accepted that these molecular alterations are mutually exclusive. Nevertheless, limited series suggest that concomitant molecular alteration can occur in lung cancer and little is known about their sensitivity to treatment. Based on a nationwide screening program conducted during one year, we aimed to analyze the largest molecular database to date for concomitant mutations in order to determine the prevalence of multiple genomic alterations in NSCLC and their impact on both prognosis and response to treatment.
Methods:
The database of Biomarker France IFCT study collecting the molecular profile of 17 664 NSCLC has been used. The prevalence of multiple alterations and of each association was calculated. Impact on prognosis (overall survival, OS), response to targeted or conventional treatments (progression free survival, PFS and objective response rate, ORR) were established and compared with the population of patients harboring single mutations and full wild-type.
Results:
We identified 162 (0.9%) patients with double genetic alterations and 3 with triple alterations. Multiple mutations involved preferentially KRAS (67.3%), PI3K (53.3%) and EGFR (42.4%). Patients with multiple alterations were male (56.4%) with a median age of 66.7 and essentially adenocarcinoma (83.6%). More never-smokers were observed in comparison with patient with singles alterations (34.7 vs. 25.8 %, p<0.001). OS was not significantly different between single and multiple alterations whatever the type of mutations. Patients with EGFR/KRAS and EGFR/PI3K mutated tumors had worse PFS after biomarker analysis than patients with EGFR single mutation (7.1 and 7.1 months vs. 14.9 months, p=0.02 and 0.002, respectively). Concomitant mutations in patients harboring ALK rearrangement had little impact on OS (17.7 months vs. 20.3 months, p=0.57) or PFS (10.3 months vs. 12.1 months, p=0.93). Patients harboring KRAS mutations with another alteration had similar OS (13.4 vs. 11.2 months, p=0.28), PFS (6.4 months vs. 7.2 months, p=0.78) and ORR to first-line chemotherapy (41.7% vs. 37.2%) to those only harboring KRAS mutations.
Conclusion:
With almost 1% of patients harboring multiple genomic alterations, the dogma of mutually exclusive mutations should be reconsidered. Double mutations do not significantly decrease OS but alter PFS under first line treatment for EGFR mutated patients. Therapies targeting the dominant oncogene remain generally active in this setting.
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OA10.07 - Report on Liquid Biopsies from Advanced Lung Adenocarcinoma Patients and Correlation with Their Tumor Biopsy Profiles (ID 4826)
12:05 - 12:15 | Author(s): E.S. Santos, L.E. Raez, L.D.C. Castillero, C. Marana, B. Hunis
- Abstract
- Presentation
Background:
Liquid biopsy (LBx) has emerged as an alternative tool for the management of advanced lung cancer patients (pts) identifying driver mutations, and hence, improving personalized medicine. There are still controversial issues such as standardization, validation of different technologies, concordance with tissue molecular profile results (TMPR), and others. LBx offers many advantages including non-invasive, bypass tumor heterogeneity, an opportunity for serial measurements to evaluate response or early recurrence, and others.
Methods:
Guardant 360 was analyzed in 100 consecutive stage IV or recurrent lung adenocarcinoma (adeno) pts. Guardant 360 is a panel of 70 genes including single nucleotide variations, amplifications, translocations, and short insertions/duplications/deletions in exons 19 and 20 of the EGFR, and others. Cell-free DNA (cfDNA) is extracted from plasma and genomic alterations are analyzed by massively parallel sequencing of amplified target genes. TMPRs from each subject was obtained or recovered for comparison with their LBx counterparts. TMPRs from this cohort was developed in different CLIA laboratories
Results:
69 pts were females; median age 72 (range, 27-99). 84/100 pts had at least 1 genomic alteration by LBx (range, 1-10). Most common abnormalities found in LBx were: TP53 (37 pts), EGFR (35 pts), NF1 (20 pts), KRAS (12 pts), MET (14 pts). From this 84 pts with + LBx results, 67 pts (80%) had TMPRs for comparison. Main reason for lack of TMPRs: insufficient tumor (19/100; 19%). For comparison between the 2 modalities, we considered all pts with available results in both tests; hence, 81 pts were used to compare tumor biopsy (TBx) vs. LBx. 37 pts out of 81 (46%) had at least 1 similar genomic abnormality found in both TBx and LBx, respectively. Most of the concordance was in EGFR alterations (19/28; 68%). LBx caught 16 additional EGFR genomic aberrations not being identified by TBx. A total of 35 EGFR genomics aberrations were identified in LBx; 16/35 EGFR mutations found in LBx were actionable and 5 of these 16 actionable EGFR mutant cases were only found in LBx not in TBx.
Conclusion:
LBx offers an alternative to identify genomic alterations. Still, insufficient tumor is the major reason for lacking of TMPRs. EGFR mutations are the most common actionable mutations found in LBx; also, it has a high correlation with TBx (68%). LBx identified more gene abnormalities than TBx, and in some cases, the actionable EGFR mutations were found only in LBx sample.
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OA10.08 - Discussant for OA10.05, OA10.06, OA10.07 (ID 7080)
12:15 - 12:30 | Author(s): F. Cappuzzo
- Abstract
- Presentation
Abstract not provided
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Author of
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MTE16 - Precision Medicine in NSCLC: Lessons Learned and Perspectives (Ticketed Session) (ID 310)
- Event: WCLC 2016
- Type: Meet the Expert Session (Ticketed Session)
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 07:30 - 08:30, Strauss 2
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MTE16.01 - Precision Medicine in NSCLC: Lessons Learned and Perspectives (ID 6568)
07:30 - 08:00 | Author(s): T. Kato
- Abstract
- Presentation
Abstract not provided
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P1.06 - Poster Session with Presenters Present (ID 458)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.06-021 - Treatment Patterns and Healthcare Resource Use from a Retrospective Cohort of Japanese Patients with Advanced Non-Small Cell Lung Cancer (ID 4632)
14:30 - 14:30 | Author(s): T. Kato
- Abstract
Background:
The treatment landscape for advanced/metastatic non-small cell lung cancer (NSCLC) has changed with the advent of targeted therapies and the use of companion diagnostics.
Methods:
The primary objective of this multi-site, retrospective, chart review study was to describe the treatment patterns, Biomarker (Bmx) testing practices and health care resource use (HCRU) in patients who initiated first line therapy (1LT) for newly diagnosed Stage IIIB/IV NSCLC between January 2011 - July 2013 in Japan. Data were analyzed descriptively. Overall survival (OS) was estimated using the Kaplan-Meier method.
Results:
Of the 175 Japanese patients 70% were male, 19% non- smokers, mean age of 68.8 years (SD=7.75), 83% stage IV and 74 % (n=129) with non-squamous (NSq) histology. 60% (n=105) received second line therapy (2LT) and 31% (n=55) received third line + therapy (3L+T). 85% (n=110) of the NSq and 40% (n=17) of the squamous (Sq) patients received at least one Bmx test. 81% (n=105) and 19% (n=25) of NSq patients, and 40% (n=17) and 24% (n=4) of Sq patients received an EGFR and ALK test, respectively. EGFR Tyrokinase Inhibitors were most commonly used among NSq EGFR mutated patients (n=44) across all lines. 86% (n=38) of the patients used Gefitinib in 1LT and Erlotinib was used in 2LT (n=11 of 30, 37%) and 3LT (n=9 of 15, 60%) patients. All ALK positive patients (n=2) in 1L received anti-ALK therapy (Crizotinib). Among NSq EGFR/ALK negative or unknown patients (n=83), 89% (n=74) received platinum combinations, most commonly carboplatin+paclitaxel (n=22, 26.5%). Single agents (n=29, 67% and n=11, 50%) were commonly used in NSq EGFR/ALK negative or unknown patients receiving 2LT (n=43) and 3LT (n=22); most commonly docetaxel (n=15, 35% & n=5, 23%). Majority of the 1LT patients with Sq histology (36/43, 84%) received platinum combinations therapy; most commonly carboplatin+paclitaxel (51%). Among 2LT, 67 % (n=20) received a single agent, most commonly docetaxel (n=14, 47%). Single agents were commonly used in 73% (n=11) of the patients receiving 3L+T. Overall, the average length of stay, regardless of line of therapy, was 24.6 days per admission. Duration of treatment was longest for 1LT (mean [SD] 140 [175] days), followed by 2LT (66 [129] days) and 3L+T (65 [83] days).Median OS for Japan from start of 1LT & 2LT was 9.9 and 4.7 months, respectively.
Conclusion:
NSq patients are frequently tested for Bmx in Japan. Treatment is personalized according to mutation status and is in concordance with recommended guidelines.
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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-027 - A Randomized Phase II Trial of S-1 plus Cisplatin or Docetaxel plus Cisplatin with Concurrent Thoracic Radiotherapy for Stage III NSCLC: TORG1018 (ID 4164)
14:30 - 14:30 | Author(s): T. Kato
- Abstract
Background:
Concurrent chemoradiotherapy (CCRT) is the current standard treatment for inoperable stage III non-small cell lung cancer (NSCLC), and a clearly superior regimen has not yet been identified. This study was conducted to evaluate cisplatin with S-1 (SP) or docetaxel (DP) with concurrent thoracic radiotherapy in patients with inoperable stage III NSCLC.
Methods:
In this open-label, non-comparative phase II trial, patients with inoperable stage IIIA/B NSCLC were randomized (1:1) to SP (S-1 40 mg/m[2] twice a day on days 1-14 and 29-42, and cisplatin 60 mg/m[2] on days 1 and 29) or DP (docetaxel 50 mg/m[2] and cisplatin 60 mg/m[2 ]on days 1 and 29), stratified by institution, gender, histology, and stage. In both arms, concurrent radiotherapy was started on day 1 (total 60 Gy in 30 fractions). After CCRT, patients in each group received two additional cycles of consolidation chemotherapy with the same regimen as that for the CCRT part. The primary endpoint was the 2-year overall survival (OS) rate, and secondary endpoints were OS, progression-free survival (PFS), toxicity profile, dose intensity and objective response rate (ORR).
Results:
Between May 2011 and August 2014, 110 patients from 19 institutions were enrolled. Finally, 106 patients (56 in each arm) were evaluable for efficacy and safety. The patient characteristics were: male/female, 83/23; median age, 65 (range 42-74) yr; performance status 0/1, 59/47; IIIA/IIIB, 59/47. After a median follow-up of 23.1 months, ORR and median PFS were 71.7% (95%CI: 57.7-83.2) and 11.5 months (95%: 9.00-14.1) in the SP arm, and 67.9% (95%CI: 53.7-80.1) and 17.2 months (95%: 9.62-24.0) in the DP arm, respectively. Grade 3-4 leukopenia (34.0%/62.3%) and neutropenia (28.3%/56.6%) were significantly higher in the DP arm than in the SP arm. Incidences of non-hematological toxicity including febrile neutropenia, anorexia, nausea, diarrhea, radiation pneumonitis and esophagitis tended to be high in the DP arm. No treatment-related death occurred.
Conclusion:
At this preliminary stage, it appears that although the DP arm may have more toxic effects than the SP arm, it has a favorable PFS. The OS data will be available soon.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-039 - Analysis of Prognostic Factor for Afatinib Treated Patients with EGFR Mutation Positive NSCLC (ID 6360)
14:30 - 14:30 | Author(s): T. Kato
- Abstract
Background:
Afatinib, known as irreversible EGFR-TKI, significantly improved PFS and OS versus cisplatin-based chemotherapy, in combined analysis of LUX-Lung 3 and 6 despite this was not proved in treatment with former reversible agents. We have tried to examine the factors correlated to improvement of survival in patients treated with afatinib compared to gefitinib or erlotinib.
Methods:
Patients who are enrolled in clinical trials from 2008 to 2014, and treated with EGFR-TKI as first line treatment were eligible. To explore the prognostic factors, we analyzed correlation of candidate factors including age, sex, clinical stage, mutation type and subsequent systemic treatments on medical record in afatinib treated group and reversible agents treated group including gefitinib or erlotinib.
Results:
Nineteen patients (5 men, 14 women) with a median age of 62 years (range, 46-88 ) were treated with EGFR-TKI as first line treatment. Twelve patients were treated with reversible TKIs, 8 with gefitinib, 4 with erlotinib. Seven patients were treated with afatinib. Median PFS for reversible TKI group versus afatinib group was 397 vs 422 days (P = 0.810). Median OS for reversible TKI group versus afatinib group was 741 vs 1380 days (P = 0.501). There is no difference between the two groups, age(P=0.147), sex(P=0.211), stage(P=0.891), and mutation type(P=0.581). Eleven patients received subsequent EGFR-TKI after first line EGFR-TKI failed as “re-challenge”, 7 patients in reversible TKI group, and 4 patients in afatinib group. There is no difference of tumor response of “re-challenge” EGFR-TKI, and duration of treatment with EGFR-TKI, in two groups.
Conclusion:
The patient treated with afatinib tends to live longer in terms of overall survival. But there were no significant correlated factor between clinical characteristics and duration of survival.
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P3.02b-124 - Efficacy of Osimertinib in Patients with Non-Small-Cell Lung Cancer (NSCLC) and Pleural Effusion (ID 5653)
14:30 - 14:30 | Author(s): T. Kato
- Abstract
Background:
Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective in patients with mutated non-small-cell lung cancer (NSCLC), pleural or pericardial effusion is a known negative factor in EGFR-TKI monotherapy. Osimertinib, a 3rd-generation EGFR-TKI is an active agent for treating EGFR T790M-positive NSCLC. We analyzed the efficacy of osimertinib in EGFR T790M-positive patients with pleural effusion.
Methods:Patients treated with osimertinib were evaluated in clinical practice following approval of the drug in Japan. Treatment responses of tumor and effusion were measured and analyzed in patients with and without pleural effusion.
Results:Twenty-five patients (7 men, 18 women) with a median age of 70 years (range, 38 – 86 years) were treated with osimertinib between 28 March and 30 June, 2016. Thirteen of the patients had no pleural effusion, of which twelve were evaluable for tumor response and all of these experienced efficacies in terms of response and stable disease. Twelve out of 25 patients had pleural effusion, of which ten patients were evaluable; of these, nine patients had no progression and one patient had progression during a short period of treatment with osimertinib. Regarding the pleural effusion in these ten patients, the effusion decreased in two patients and, was stable in three patients; in five patients, these was a slight or moderate increase despite daily administration of osimertinib. The long-term effects of treatment with osimertinib will be presented in detail at the meeting. Figure 1
Conclusion:Although an active agent in clinical practice, osimertinib might not provide an early response for pleural effusion.
