Virtual Library

  • +

    P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
    • +

      P1.01-017 - Two Cases of NSCLC with EGFR Exon 20 Insertions with Major Clinical Response to Cetuximab-Containing Therapies (ID 653)

      09:30 - 17:00  |  Author(s): C.M. Vanderbilt, E.C. Fulchiero, R.J. Hoyer, D.L. Aisner, R.C. Doebele

      • Abstract
      • Slides

      Background:
      Lung tumors with EGFR Exon 20 mutations, particularly insertions between the amino acids Y764 and V774, present a major challenge for treatment. These mutations are known to confer resistance to current EGFR specific tyrosine kinase inhibitors (TKI). The mechanism of this resistance is described by Yasuda et al. as a “wedge” formed by the aberrant amino acids locking the C-helix in an inward, active position. This structural aberration prevents the TKI from accessing the critical pocket within the protein and inhibiting kinase activity. Without the ability to treat these tumors with TKIs, alternate treatments need to be pursued.

      Methods:
      We present, as index cases, two patients with metastatic lung adenocarcinomas demonstrating TKI unresponsive insertions in exon 20. Both patients had exuberant clinical and radiographic responses to cetuximab, an EGFR specific monoclonal antibody.

      Results:
      The first patient is a 39 year old male never-smoker with lung adenocarcinoma. The disease had progressed prior to molecular identification of the EGFR mutation, and the patient developed bilateral lung disease and metastatic lymph node and brain lesions. An exon 20 EGFR mutation (p.N771_P772insPHGH c.2313_2314insCCCCACGGGCAC) was identified. Following 4th line therapy with combination chemiotherapy plus cetuximab, the tumor burden was dramatically decreased and the patient had markedly improved functional status with the ability to return to employment. The second patient is a 71 year old male never-smoker with lung adenocarcinoma. The disease progressed and the patient developed widely metastatic disease. An exon 20 EGFR mutation (P770_N771insNPP) was identified. The patient was treated with combination cetuximab and afatinib therapy and experienced a dramatic decrease in lung and metastatic tumor burden with improved functional status.

      Conclusion:
      Cetuximab-containing therapeutic regimens may be a viable therapy for what previously have been considered treatment resistant molecular insults. Additional cases of these mutations and treatment with cetuximab are needed to demonstrate that these results are reproducible and that they warrant study in prospective clinical trials.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    OA10 - EGFR Mutations (ID 382)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Biology/Pathology
    • Presentations: 1
    • +

      OA10.01 - Comprehensive Genomic Profiling and PDX Modeling of EGFR Exon 20 Insertions: Evidence for Osimertinib Based Dual EGFR Blockade (ID 4375)

      11:00 - 12:30  |  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
      • Slides

      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.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.01-61 - Clinical Characterization of ERBB2 Exon 20 Insertions and Heterogeneity of Outcomes to Afatinib in Chinese Lung Cancers (ID 13066)

      16:45 - 18:00  |  Presenting Author(s): Zhefeng Liu  |  Author(s): Yi Hu, Lin Wu, Jun Cao, Zhe Yang, Cheng Zhi Zhou, Liming Cao, Hao Wu, Haibo Shen, Meiling Jin, Yong Zhang, Xinru Mao, Jianxing Xiang, Ke Ma, Bing Li, Tengfei Zhang

      • Abstract
      • Slides

      Background

      Background: Human epidermal growth factor 2 (HER2, ERBB2) gene alterations have been identified as oncogenic drivers in 2-5% of lung cancers. ERBB2 In-frame insertions in exon 20 (20ins) lead to constitutive activation of receptor and downstream pathways. However, response heterogeneity of different exon 20 insertions to ERBB2 inhibitor afatinib exists. In vitro and structural modeling results suggested that Glycine778 may facilitate inhibitor binding to ERBB2. In this study, our aim was to improve our understanding of clinical characteristics in ERBB2-mutated Chinese lung cancer and investigate the clinical outcomes of specific ERBB2 exon 20 insertions in response to afatinib.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Methods: We reviewed 7520 lung cancer patients whose tissue or plasma biopsies were sequenced in a CLIA-certified sequencing laboratory between 2015 to 2018. Clinical records of 19 patients (18 adenocarcinomas and 1 squamous cell carcinoma) with several different ERBB2 20ins after afatinib treatment were collected for clinical outcomes evaluation.

      4c3880bb027f159e801041b1021e88e8 Result

      Results: ERBB2 20ins were identified in 2.27% (171/7,520) in this Chinese lung cancer cohort. It occurred with a high proportion in females with adenocarcinoma histology. 11.7% (20/171) ERBB2 20ins-positive patients harbored concomitant ERBB2 amplification. Y772_A775dup (119/171, 69.6%) was the most frequently occurred 20ins subtype, followed by G778_P780dup (18/171, 10.5%). For the 19 patients treated with afatinib, they had a median PFS of 4.5 months and median OS of 11.5 months. The overall response rate in this cohort was 15.8% (3/19) and disease control rate was 68.4% (13/19). Next, we interrogated the clinical outcomes of specific 20ins subtype responding to afatinib. We found that patients harboring G778_P780dup (G778) achieved longer median PFS (10 vs 3.3 months, p=0.32) and median OS (19.7 vs 7 months, p=0.16) than non-G778 patients, consisting with in vitro results. Although statistical significance was not achieved due to limited number of G778_P780dup patients, this result warranted further investigation into this phenomenon. Moreover, to the best of our knowledge, we identified the first case of a lung squamous cell carcinoma patient harboring ERBB2 20ins from this cohort. He displayed favorable response to afatinib and achieved partial response with significant tumor shrinkage.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Conclusion: We interrogated the characteristics of ERBB2 exon 20 insertions in a large cohort from single ethnicity. It demonstrated the response heterogeneity to afatinib among different ERBB2 exon 20 insertion subtypes. It highlighted the importance to correlate drug efficacy with specific ERBB2 exon 20 insertion variants in clinical application.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.13-42 - Activity of Novel HER2 Inhibitor, Poziotinib, for HER2 Exon 20 Mutations in Lung Cancer and Mechanism of Acquired Resistance (ID 12717)

      16:45 - 18:00  |  Presenting Author(s): Takamasa Koga  |  Author(s): Yoshihisa Kobayashi, Kenji Tomizawa, Yuichi Sesumi, Toshio Fujino, Masaya Nishino, Shuta Ohara, Masato Chiba, Masaki Shimoji, Kenichi Suda, Toshiki Takemoto, Tetsuya Mitsudomi

      • Abstract

      Background

      Oncogenic HER2 mutations are present in 2-4% of adenocarcinoma of the lung. However, clinical trials of HER2 inhibitors such as afatinib or neratinib has been unsatisfactory. Recently, a novel HER2 inhibitor, poziotinib has been developed and clinical trial results are being expected. Here, we evaluated poziotinib in comparison with pre-existing TKIs using Ba/F3 system. We also derived resistant clones against poziotinib and investigated their resistant mechanism.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We introduced three common HER2 mutations into Ba/F3 cells (i.e. G776delinsVC (VC), A775_G776insYVMA (YVMA) and P780_Y781insGSP (GSP)) which account for 13, 72, 9% of HER2 mutations in human lung cancer, respectively. We defined sensitivity index (SI) as an IC90divided by trough concentration of a given drug at the recommended dose for humans in the literature, as a surrogate for drug activity in humans. Poziotinib activity was compared with 8 TKIs (afatinib, osimertinib, erlotinib, neratinib, lapatinib, dacomitinib, irbinitinib, and AZ5104). In addition, we created resistant clones by exposing poziotinib in the presence of N-ethyl-N-nitrosourea (ENU) and HER2 secondary mutations were searched.

      4c3880bb027f159e801041b1021e88e8 Result

      All drugs but lapatinib showed the highest activity against VC (Table). In contrast, YVMA was most resistant in all but neratinib and poziotinib. For most common YVMA, poziotinib was the only drug that had SI of less than 10 (Table). Furthermore, poziotinib was most potent for VC and GSP except dacomitinib for GSP (Table). We established 19 poziotinib-resistant clones, all of which harbored C805S secondary mutation of the HER2 gene homologous to C797S of the EGFR gene.

      Ctrough [nM] YVMA VC GSP
      Afatinib 69 28 5.4 12
      Dacomitinib 166 20 4.4 6.6
      Erlotinib 2969 337 22 98
      Osimertinib 400 40 4.5 30
      Neratinib 100 11 11 28
      Lapatinib 516 133 117 91
      Poziotinib 20 6.0 2.7 10
      Irbinitinib 520 34 33 16
      AZ5104 50 60 8.0 48

      8eea62084ca7e541d918e823422bd82e Conclusion

      Poziotinib showed the most potent activity against HER2 exon 20 mutations. We also found that secondary C805S HER2 mutation was the common mechanism of acquired resistance, which most likely inhibit covalent binding of poziotinib with HER2.

      6f8b794f3246b0c1e1780bb4d4d5dc53

    • +

      P1.13-44 - Safety, PK, and Preliminary Antitumor Activity of the Oral EGFR/HER2 Exon 20 Inhibitor TAK-788 in NSCLC (ID 12373)

      16:45 - 18:00  |  Presenting Author(s): Joel W. Neal  |  Author(s): Robert C. Doebele, Gregory J Riely, Alexander Spira, Leora Horn, Zofia Piotrowska, Daniel B Costa, Steven Zhang, Dean Bottino, Jian Zhu, David Kerstein, Shuanglian Li, Pasi A Jänne

      • Abstract
      • Slides

      Background

      TAK-788 (AP32788) is an investigational tyrosine kinase inhibitor (TKI) with potent, selective preclinical activity against activating EGFR and HER2 mutations, including exon 20 insertions. We report early results of a phase 1/2 first-in-human, open-label, multicenter study of TAK-788 (NCT02716116).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with advanced non-small cell lung cancer (NSCLC) refractory to standard therapy received daily oral doses (5–120 mg) of TAK-788 in the ongoing dose-escalation phase (3+3 design). Preliminary antitumor activity (by RECIST v1.1), safety, and PK are reported for patients who received ≥1 dose.

      4c3880bb027f159e801041b1021e88e8 Result

      As of 8-Sep-2017, 34 patients (median age, 60 y; female, 65%; ≥2 prior anticancer therapies, 88%; Table) were treated with TAK-788; 10 remain on treatment at data cutoff. AUC0‑24,ss increased in a dose-proportional manner over the dose range evaluated; the effective t1/2 was ~16 (range 6–28) h. The most common treatment-emergent AEs (TEAEs; ≥20%) were diarrhea (47%), nausea (26%), and fatigue (21%). Grade ≥3 TEAEs in ≥2 patients (excluding disease progression) were dyspnea (n=3, 9%) and anemia, asthenia, dehydration, lung infection, pleural effusion, pneumonia, and pneumonitis (n=2 each, 6%). Two DLTs, both pneumonitis, were reported (80 mg, grade 3; 120 mg, grade 5). Of 14 evaluable patients, 3 had PR (80 mg, n=2, both confirmed; 120 mg, single PR awaiting confirmation), 6 had SD (40 mg, n=3; 80 mg, n=2; 120 mg, n=1), and 5 had PD as best response (40 mg, n=3; 80 mg, n=1; 120 mg, n=1). All patients with PR had EGFR exon 20 insertions.

      8eea62084ca7e541d918e823422bd82e Conclusion

      TAK-788 exhibits antitumor activity in patients with EGFR exon 20 insertions with an AE profile consistent with other EGFR TKIs. Phase 2 will begin after determination of the RP2D, with 4 molecularly defined cohorts in NSCLC. Updated data will be presented, including the recommended phase 2 dose (RP2D).

      Baseline Characteristics

      5 mg

      (n=4)

      10 mg

      (n=5)

      20 mg

      (n=5)

      40 mg

      (n=6)

      80 mg

      (n=7)

      120 mg

      (n=7)

      Total

      (n=34)

      Mutation type,a %

      Common EGFR mutations (exon 19 deletion / L8585R) 25 20 0 0 0 0 6
      EGFR-T790M+ 0 0 0 0 14 0 3
      EGFR exon 20 insertion 50 40 60 83 71 57 62
      HER2 0 20 40 17 14 29 21
      a One patient (20 mg) had both EGFR and HER2 mutations; 1 patient (80 mg) had EGFR exon 20 insertion + T790M.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    P1.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 947)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.15-05 - The Frequency and Spectrum of EGFR Exon 20 Insertions in NSCLC: A Global Literature Review (ID 11975)

      16:45 - 18:00  |  Presenting Author(s): Victoria Crossland  |  Author(s): Shuanglian Li, Aaron Galaznik

      • Abstract
      • Slides

      Background

      There are limited epidemiological data on non-small cell lung cancer (NSCLC) patients with non-classical (uncommon) epidermal growth factor receptor (EGFR) mutations. In light of ongoing development of TAK-788, we describe the global frequency and spectrum of EGFR exon 20 insertions in NSCLC based on a comprehensive literature review as well as highlight possible regional variations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A literature search was conducted to identify publications reporting the frequency of EGFR exon 20 insertions in unselected NSCLC patients. PubMed and ASCO, ESMO, and IASLC meeting abstracts were searched up to April 2018 using the following keywords: non-small cell lung cancer, epidermal growth factor receptor, exon 20, insertions and uncommon mutations. Only publications in English were included. The pooled frequency of EGFR exon 20 insertions for each country were determined, and insertion variants (where available) were described at the global level.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 26 studies from 25 countries were included, reporting on 569 patients with EGFR exon 20 insertions among 41,321 NSCLC patients. The highest mutation frequency was seen in China (2.9%) and the lowest in Indonesia (0.1%). When pooled by country, exon 20 insertions were found in 0.1−2.1% of all NSCLC.

      frequency of egfr exon 20 insertions in patients with nsclc.jpg

      Over 50 insertion variants were reported, covering amino acids 761−774. The most commonly detected mutations included D770_N771insSVD, V769_D770InsASV, H773_V774InsH, H773_V774insNPH, and A763_Y763insFQEA.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The frequency of EGFR exon 20 insertions was 0.1−2.1% of NSCLC patients, with a high variability in both length and position of insertions within exon 20. Currently, available data are sparse and come primarily from studies based on single-center experiences, with data gaps across several large geographic regions and populations. Results also indicate a need to further explore underlying geographic variations in epidemiology. Larger, multi-center global studies will further help to refine the frequency of exon 20 insertions and other uncommon mutations in NSCLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    OA07 - Precision Medicine Involves Biology and Patients (ID 132)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • +

      OA07.03 - Clinical Outcome of Non-Small Cell Lung Cancer with EGFR/HER2 Exon 20 Insertions Identified in the LC-SCRUM-Japan (Now Available) (ID 629)

      11:00 - 12:30  |  Presenting Author(s): Hibiki Udagawa  |  Author(s): Shingo Matsumoto, Yuichiro Ohe, Miyako Satouchi, Naoki Furuya, Young Hak Kim, Takashi Seto, Kenzo Soejima, Daisuke Hayakawa, Terufumi Kato, Shingo Miyamoto, Kadoaki Ohashi, Sho Saeki, Hiromitsu Ohta, Daichi Fujimoto, Akimasa Sekine, Kiyotaka Yoh, Koichi Goto

      • Abstract
      • Presentation
      • Slides

      Background

      In-frame insertions in exon 20 (Ex20ins) of EGFR/HER2 occur in 2-5 % of non-small cell lung cancer (NSCLC). There is no approved targeted therapy for patients with these mutations. Historical control data would be valuable for the development of novel targeted therapies for these rare cancers.

      Method

      A nationwide genome screening project in Japan (LC-SCRUM-Japan) has been established for the development of molecular-targeted therapies for lung cancers. In this project, 161 cancer-related genes have been analyzed by a next-generation sequencing (NGS) system, Oncomine™ Comprehensive Assay. The therapeutic efficacy and survival of the patients with non-squamous (non-sq) NSCLC harboring EGFR/HER2 Ex20ins were evaluated using a large-scale clinico-genomic database in the LC-SCRUM-Japan.

      Result

      A total of 3441 advanced non-sq NSCLC patients were successfully analyzed from 2015 to 2018. EGFR Ex20ins were detected in 73 patients (2%; M766_A767insASV/A767_S768insSVD/H773_V774insH/D770_N771insNPH/N771_P772insPH/others=22/17/5/4/4/21) and HER2 Ex20ins were detected in 128 patients (4%; A775_G776insYVMA/G776delinsVC/P780_Y781insGSP/others=95/16/10/7). The median age of the patients was 62 (range, 33-90) years. Eighty-one patients (40%) were male and 114 (57%) were never smoker. Two-hundred patients (99%) were diagnosed as adenocarcinoma and 1 as adenosquamous-cell carcinoma. Based on our database, the median overall survivals in patients with EGFR Ex20ins were 22.4 (95%CI, 15.3-36.8) months, and those with HER2 Ex20ins were 18.8 (13.6-30.3) months. In the patients with EGFR/HER2 Ex20ins, the objective response rate (ORR) and median progression-free survivals (mPFS) of 1st-line platinum-containing chemotherapies were 32% and 6.0 (5.7-7.0) months, respectively. The ORR and mPFS of docetaxel with or without ramucirumab were 26% and 5.1 (3.8-5.9) months, respectively. The ORR and mPFS of PD-1 inhibitor were 0% and 2.0 (1.6-2.6) months, respectively. No significant difference in the therapeutic efficacy of these drugs was observed between the patients with EGFR Ex20ins and HER2 Ex20ins. In 19 patients with EGFR Ex20ins treated with 1st/2nd generation EGFR-TKIs, the ORR was 5% (a M766_A767insASV-positive tumor responded to afatinib) and the mPFS was 2.1 (1.3-4.2) months.

      Conclusion

      The patients with EGFR/HER2 Ex20ins-positive NSCLC showed poor responses to PD-1 inhibitors and 1st/2nd generation EGFR-TKIs. These historical data are highly informative in evaluating the efficacy of novel targeted therapies for EGFR/HER2 Ex20ins-positive NSCLC.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 4
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.01-89 - A Multicenter Phase 1/2a Trial of CLN-081 in NSCLC with EGFR Exon 20 Insertion Mutations (ID 488)

      09:45 - 18:00  |  Presenting Author(s): Zofia Piotrowska  |  Author(s): David Planchard, Myles Steven Clancy, David Witter, Leigh Zawel, Helena A Yu

      • Abstract

      Background

      First and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are largely ineffective against EGFR exon 20 insertion mutations (ins20) and, while several novel agents targeting EGFR ins20 are in development (poziotinib, TAK-788), preliminary reports suggest that EGFR-related adverse events are common and may limit long-term efficacy (Heymach, WCLC 2018, Neal WCLC 2018). Targeted therapies which are safe and effective in patients with EGFR ins20 are needed. CLN-081 (also known as TAS-6417) is a novel, orally available EGFR TKI that selectively inhibits ins20 mutant EGFRs (Mol Cancer Ther 2018; 17:1648). In a cell-based assay using genetically engineered cell lines, CLN-081 potently inhibited intracellular phosphorylation of a wide spectrum of ins20 mutant EGFRs. The selectivity for mutant over wild type EGFR (WT/mut ratio) ranged from 4 to 134-fold depending on the specific mutation, representing an unprecedented level of mutant specificity.

      Method

      This is an adaptive phase 1/2a trial evaluating CLN-081 as monotherapy in advanced non-small cell lung cancer (NSCLC) harboring EGFR ins20. Dose escalation will proceed initially according to an accelerated titration (AT) design, converting to a rolling six (R6) design based upon pre-specified safety criteria. Cohort expansion in Phase 1 can occur at one or more doses where responses are observed in R6 cohorts. Transition from Phase 1 into Phase 2a is based upon a Simon-Two Stage design. The starting dose will be 60mg. Once daily and twice daily dosing will be explored. Approximately 90 patients will be enrolled. Eligible patients will have advanced, exon 20 insertion mutation positive NSCLC, and at least one prior platinum containing treatment regimen. EGFR ins20 will be identified based on local testing (tissue or plasma). Patients who have discontinued a previous EGFR TKI due to progressive disease will be allowed in AT dose escalation cohorts but will be excluded from R6, and the Phase 1 and 2a expansion cohorts. The primary objectives in Phase 1 are to demonstrate safety and determine the maximum tolerated dose. Secondary Phase 1 objectives include evaluation of PK and preliminary efficacy. The primary objectives in Phase 2a are to define the recommended phase 2 dose and evaluate the overall response rate. The secondary Phase 2a objectives include additional measures of response and confirmation of CLN-081’s safety profile.

      Result

      Section not applicable

      Conclusion

      Section not applicable

    • +

      P1.01-94 - JNJ-61186372, an EGFR-cMet Bispecific Antibody, in EGFR Exon 20 Insertion-Driven Advanced NSCLC (ID 1802)

      09:45 - 18:00  |  Presenting Author(s): Byoung Chul Cho  |  Author(s): Jiyeon Yun, Han Na Kang, Soo-Hwan Lee, Chae-Won Park, Seo-Yoon Jeong, Min Hee Hong, Hye Ryun Kim, Meena Thayu, Joshua C Curtin, Roland E Knoblauch, Matthew V Lorenzi, Amy Roshak

      • Abstract

      Background

      JNJ-61186372 (JNJ-372), a bispecific antibody that targets the EGFR and cMet receptors, is currently being explored in a first-in-human study in patients with non-small cell lung cancer (NSCLC). Preliminary JNJ-372 clinical data have suggested activity in patients with diverse EGFR mutations, including Exon 20 insertions (Exon20ins), which carry primary resistance to tyrosine kinase inhibitors (TKIs; Cho BC et al. Ann Oncol 2018;29(suppl_8):mdy292.118). To better understand the mechanism of JNJ-372 activity in this patient population, we conducted preclinical studies exploring the activity of JNJ-372 in different EGFR Exon20ins models.

      Method

      BaF3 cells were transduced with retrovirus expressing various EGFR Exon20ins, as described. Cell titer glo assays were used to measure cell proliferation; western blot analysis was used to study EGFR and cMet signaling cascade events. For mouse tumor models, JNJ-372 was administered i.p. daily at 10mg/kg or 30mg/kg. Referenced patients with Exon20ins disease were administered 1050mg JNJ-372 i.v. weekly for the first 4-week cycle, then biweekly for each subsequent cycle (Park et al. J Thorac Oncol 2018;13:S344-5).

      Result

      In a dose-dependent manner, JNJ-372 inhibited the growth of BaF3 cells harboring diverse Exon20ins mutations. Mechanistic assays revealed down-modulation of EGFR and cMet receptor levels and decreases in phospho-EGFR and cMet, as well as inhibition of downstream signaling events including p-ERK, p-Akt and p-S6. Cleaved caspase-3 and BIMEL were upregulated at antiproliferative doses, suggesting caspase-mediated cell death as part of the mechanism of action. JNJ-372 demonstrated corresponding antitumor activity in PDC and PDX models harboring different Exon20ins mutations with concomitant inhibition of EGFR signaling and induction of apoptosis. In the ongoing first-in-human trial, two patients with Exon20ins disease (P772_H773insPNP and H773delinsNPY) continue to demonstrate durable clinical benefit (13 and 22 cycles), with maximum tumor reductions of –23% and –63%, respectively, as demonstrated by baseline and postbaseline CT scans.

      Conclusion

      In EGFR Exon20ins disease, JNJ-372 demonstrates preclinical antitumor activity and initial clinical responses. Preclinically, JNJ-372 induces antitumor activity in models of EGFR Exon20ins disease by decreasing EGFR and cMet receptor levels, inhibiting downstream signaling cascades, and activating apoptotic signaling. These results provide an understanding of the activity of JNJ-372 being observed in the ongoing clinical study and support the continued examination of JNJ-372 in NSCLC patients with Exon20ins and other EGFR mutations.

    • +

      P1.01-126 - The Co-Occurring Genomic Landscape of ERBB2 Exon 20 Insertion in Non-Small Cell Lung Cancer (NSCLC) and the Potential Indicator of Response to Afatinib (Now Available) (ID 1284)

      09:45 - 18:00  |  Presenting Author(s): Bo Yuan  |  Author(s): Jun Zhao, Chengzhi Zhou, Xiumei Wang, Bo Zhu, Minglei Zhuo, Cuihua Yi, Hua Zhang, Xilin Dong, Jiemei Feng, Yunpeng Yang, Wangyan Zhou, Zhengtang Chen, Sheng Yang, Yanjun Zhang, Xinghao Ai, Kehe Chen, Xuefan Cui, Difa Liu, Wei Wu, Chunmei Shi, Lian-peng Chang, Jin Li, Rongrong Chen, Shuanying Yang

      • Abstract
      • Slides

      Background

      Human epidermal growth factor receptor 2 (ERBB2, HER-2) 20 exon insertion (ERBB2ex20ins) has been identified as an oncogenic driver in lung cancer, for which no valid therapy is currently approved. Concurrent alterations may elucidate its refractory features. Previous studies on Afatinib, a pan-ERBB inhibitor, have revealed an inconsistent clinical activity of it for this group of patients.

      Method

      Plasma or tissue samples of 112 patients with ERBB2ex20ins were performed next generation sequencing (NGS) for 59 or 1021 cancer-related genes in a Clinical Laboratory Improvement Amendments-certified Laboratory from July 2016 to December 2018. The sequencing data of MSKCC Cohort was downloaded from the public Cancer Genome Atlas Database. The clinical outcomes of 18 patients receiving Afatinib treatment were collected by each contributing doctor in charge and pooled for analysis.

      Result

      Among the 112 patients, most of cases were female (54%, 60/112) and adenocarcinoma (68%, 76/112). Considering the insertions sites, three subtypes were A775ins (71%; 79/112), G776indel (17%; 19/112) and P780ins (12%; 14/112) in the order of frequency. 80.4% (90/112) of patients had at least one additional alteration. The most frequent co-occurring genes were TP53 (66.1%, 74/112), LRP1B (18.2%, 10/55), EPHA5 (9.1%, 5/55), MLL3 (9.1%, 5/55) and RB1 (8.0%; 9/112). Putative other driver aberrations were mutually exclusive from ERBB2ex20ins. Furthermore, cell cycle pathway was the most commonly involved pathway (84.0%; 94/112) of all the concurrent genes. No substantial differences of concurrence in genomic or pathway level were observed among the three ERBB2 insertion subtypes. The co-occurring genomic feature of ERBB2ex20ins in Our Cohort of Chinese people had an overall strong concordance with the MSKCC Cohort from the United States (R2=0.74, P<0.01). For the prognosis, patients had a worse OS when co-occurring mutation in TP53 [median OS:14.5m (95%CI: 12.7m-16.3m) vs 30.3m (95% CI: not reached)], while the OS was not significantly different among three subtypes. The median duration time for patients with disease control of Afatinib was 4.5 months (95%CI: 3.6m-5.4m; range: 2.5m-13.4m). Of note, ERBB2ex20ins in subclonal status was a significantly independent factor relating to shorter PFS of Afatinib [median PFS: 1.2m (95%CI: 0.8-1.6m) vs 4.3m (95%CI: 3.3m-5.3m), P<0.05]. Dynamic detection in two patients found ERBB2 amplification may be a resistance mechanism for Afatinib.

      Conclusion

      Concurrence of genetic alterations in NSCLC patients with ERBB2ex20ins was common. The complex genomic characteristic should be fully considered by stratifying patients according to potentially relevant co-mutations other than ERBB2 insertion sites in the designing regimens for them. In addition, the therapeutic effect of Afatinib on patient with ERBB2ex20ins is limited, the clonal status of ERBB2ex20ins may be an important factor with prognosis value.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

    • +

      P1.01-127 - Antitumor Activity of the Oral EGFR/HER2 Inhibitor TAK-788 in NSCLC with EGFR Exon 20 Insertions (ID 1302)

      09:45 - 18:00  |  Presenting Author(s): Gregory J Riely  |  Author(s): Joel W Neal, D. Ross Camidge, Alexander Spira, Zosia Piotrowska, Leora Horn, Daniel B Costa, Anne Tsao, Jyoti D Patel, Shirish Gadgeel, Lyudmila Bazhenova, Viola W. Zhu, HOWARD WEST, Sylvie Vincent, Jian Zhu, Shu Jin, Steven Zhang, Shuanglian Li, Pasi A Jänne

      • Abstract
      • Slides

      Background

      We report results of a phase 1/2 open-label, multicenter study of TAK-788 (NCT02716116), an oral investigational EGFR/HER2 inhibitor.

      Method

      Patients with advanced, previously treated NSCLC received daily TAK-788 in dose escalation and expansion cohorts based on tumor genotype. Antitumor activity was determined for patients with EGFR exon 20 insertions who received TAK-788 160 mg QD. Safety is reported for all patients across all doses and at 160 mg. To improve gastrointestinal tolerability, food intake instructions in this ongoing study were amended to allow for administration with or without a low-fat meal based on emerging clinical pharmacokinetic data in a healthy volunteer study (data on file).

      Result

      As of 14 Sep 2018, 101 patients (median age, 61 y; female, 70%; ≥2 prior anticancer therapies, 76%; brain metastases, 53%) were treated with TAK-788 at 5–180 mg QD. RP2D was determined to be 160 mg QD. 28 patients with EGFR exon 20 insertions were treated with 160 mg QD during dose escalation or in expansion cohort 1 (3.6 months on treatment; 3.8 treatment cycles [medians]); 24 patients remain on treatment. At data cutoff, best response (RECIST v1.1) among 26 patients with ≥1 disease assessment was PR, n=14; SD, n=9; and PD, n=1 (objective response rate, 54%; 95% CI: 33.4%–73.4%); 2 patients were unevaluable. 7/14 objective responses (all PR) were confirmed (6 awaiting confirmation; 1 unconfirmed PR at 160 mg QD); median time to response in these 14 patients was 56 days. 23/26 patients (89%; 95% CI: 69.9%–97.6%) achieved disease control. 23/24 evaluable patients with EGFR exon 20 insertions treated at 160 mg QD had decreased target lesion measurements (median best percent change, -32.6% [-79.1%–3.8%]). Most common TEAEs (≥20%) in patients treated with 160 mg QD: diarrhea (85%), rash (43%), nausea (41%), vomiting (30%), decreased appetite (28%), stomatitis (22%); grade ≥3 TEAEs (≥5%): diarrhea (26%); hypokalemia, nausea, stomatitis (7% each). Among patients treated with 160 mg QD, median dose intensity was 93%, rate of dose reduction due to AEs was 21.7%, and rate of treatment discontinuation due to AEs was 10.9%. There was no clear trend that response to TAK-788 was enriched in any single EGFR exon 20 insertion variant.

      Conclusion

      In NSCLC patients with EGFR exon 20 insertions, TAK-788 demonstrated antitumor activity and a safety profile consistent with other EGFR TKIs.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    P1.09 - Pathology (ID 173)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.09-03 - Clinicopathological Characteristics for NSCLC Harboring EGFR Exon 20 Insertion (ID 1211)

      09:45 - 18:00  |  Presenting Author(s): Kei Morikawa  |  Author(s): Kazutaka Kakinuma, Takeo Inoue, Masamichi Mineshita

      • Abstract

      Background

      For the majority of EGFR-mutant NSCLC patients harboring exon 19 deletion or exon 21 L858R, EGFR-TKIs are key therapies for outstanding anti-tumor effects. However, for the population harboring minor mutations, clinical benefit of EGFR-TKIs are controversial. Specifically, exon 20 insertion is acknowledged as a poor prognostic mutation type compared to other minor mutations. There are few reports describing clinicopathological characteristics harboring exon 20 insertion NCSLC.

      Method

      We retrospectively analyzed patients harboring EGFR exon 20 insertion at our institution over 3 years. Clinical testing for the detection of EGFR mutations was cobas® EGFR Mutation Test v2. We evaluated pathological features for diagnostic specimens or re-biopsy samples, CT or PET images for the detection of primary lesions or metastatic locations.

      Result

      A total of 213 EGFR-mutant adenocarcinomas were reviewed for the study and screened. Of these, 19 were positive for exon 20 insertion (8.9%). Of 19 cases, 13 displayed advanced stage while 6 cases were classified as early stage. Compound major mutation was detected in 26.3% (3 cases were exon 19 deletion; 2 cases were exon 21 L858R). In advanced cases, the location of primary lesions was found mainly in the subpleural domain (84.6%), and pleural dissemination was confirmed in 77%. The majority of cases included pleural effusion. Furthermore, 70% contained mucinous type pathologically in advanced cases. In total, more than half of the cases showed well-differentiated subtypes pathologically, which was contrary to a past report1).

      Conclusion

      Contrary to a past report, EGFR exon 20 insertion in adenocarcinoma often showed pathologically mucinous and well-differentiated subtypes. For clinical characteristics, especially in advanced stage, pleural dissemination and effusion were observed with high frequency, which might be due to the primary lesion often located in the subpleural domain.

      1) Mol Cancer Ther; 2012(2); 2209

  • +

    P1.14 - Targeted Therapy (ID 182)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.14-52 - Clinical Response to Osimertinib in a Patient with Metastatic NSCLC Harboring EGFR A763_Y764insFQEA Exon 20 Insertion Mutation: A Case Report (Now Available) (ID 1268)

      09:45 - 18:00  |  Presenting Author(s): Gabriela Liliana Bravo Montenegro  |  Author(s): Chul Kim

      • Abstract
      • Slides

      Background

      Epidermal growth factor receptor (EGFR) exon 20 insertion mutations represent approximately 4-10% of EGFR-mutant non-small-cell lung cancer (NSCLC). The majority of EGFR exon 20 insertion mutations do not respond to approved EGFR tyrosine kinase inhibitors (EGFR-TKIs). Preclinical data suggest that EGFR A763_Y764insFQEA mutation is associated with sensitivity to EGFR-TKI therapy.

      A few case reports have shown that patients with this rare variant of EGFR exon 20 insertion mutation may respond to first- and second-generation EGFR-TKIs. However, efficacy of the third-generation EGFR-TKI osimertinib against the EGFR A763_Y764insFQEA mutation has not been described. Here, we present a patient with metastatic NSCLC harboring EGFR A763_Y764insFQEA alteration treated with osimertinib.

      Method

      A 56-year-old never-smoker Asian female presented with complete atelectasis of the left upper lobe, a left circumferential pleural effusion, and diffuse osseous sclerotic lesions. Pathology confirmed the diagnosis of metastatic lung adenocarcinoma. Circulating tumor DNA (ctDNA) assay utilizing InVisionSeqTM Tagged-Amplicon next-generation sequencing (NGS) identified EGFR A763_Y764insFQEA, MET amplification, and TP53 G266*. The patient was started on osimertinib 80 mg once a day. Later, tumor NGS came back positive for EGFR A763_Y764insFQEA, TP53 G266*, and BRCA-2 A2351G.

      Result

      The patient’s symptoms of cough and shortness of breath started to improve shortly after initiation of osimertinib. A CT scan of the thorax and abdomen obtained 5 weeks after starting osimertinib showed improvement in aeration of the previously collapsed left upper lobe, visualization of a 1.9 x 1.4 cm spiculated left upper lobe lung mass, improved infiltrative soft-tissue in the left hilum, and improved partially loculated left pleural effusion, suggesting response to osimertinib.

      Conclusion

      In this patient with the EGFR A763_Y764insFQEA mutation, osimertinib has shown effectiveness as monotherapy, suggesting it could serve a viable therapeutic treatment option in NSCLC with this rare variant of exon 20 insertion mutations. Future studies should validate this finding.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.

  • +

    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 3
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
    • +

      P2.01-51 - Next-Generation Sequencing for Effective Detection of Various EGFR Exon 20 Insertions (E20ins) in Non-Small Cell Lung Cancer (NSCLC) (ID 1750)

      10:15 - 18:15  |  Presenting Author(s): Inhwan Hwang  |  Author(s): Sang-we Kim, Sung-Min Chun, Shinkyo Yoon, Dae Ho Lee

      • Abstract

      Background

      Epidermal growth factor receptor (EGFR) E20ins are known as uncommon EGFR mutation and relatively insensitive to current EGFR tyrosine kinase inhibitors (TKIs). However, recent newer TKIs such as poziotinib show good clinical activity against them. Thus, we further explored the rate of EGFR E20ins and their clinical characteristics

      Method

      Between March 2017 and October 2018, 488 NSCLC tumor specimens were examined with OncoPanel AMC version3 which is a Next-generation sequencing (NGS) based assay for the detection of single-nucleotide variants, insertions, deletions, copy number alterations and structural variants across 382 genes. Peptide Nucleic Acid (PNA) clamping method version2 is to detect EGFR mutations using allele specific polymerase chain reaction and 6 variants of E20ins could be detected by it. We analyzed those NGS results and they were compared with PNA clamping method results if examined previously. Clinical characteristics were also reviewed.

      Result

      Among 488 patients, 143 showed EGFR mutations;16 patients showed wide variety of E20ins, while 59, 54 and 14 patients showing exon 19 deletion, L858R, and other rare EGFR mutations, respectively. Thus, the rate of E20ins was 11.2% of all EGFR mutations. For those 16 patients with E20ins, PNA clamping method failed to detect E20ins EGFR mutation in 8 patients (50%). Male/Female ratio was 7/9. Median age was 57 years (25-76 years). The rate of non-smoking was 68.8%. First-line platinum based regimen were given in 10 patients with 2.5 months of median progression free survival (PFS), while first-line EGFR TKIs were given in 5 patients with 2.3 months of median PFS. Poziotinib was provided to 2 patients later and they showed stable disease and partial remission.

      Conclusion

      EGFR E20ins were detected in 11.2% of EGFR-mutant NSCLC by OncoPanel AMC version3, and it was twice the rate by PNA clamping method. Clinically those patients showed lack of response to current EGFR TKIs. Poziotinib is a new EGFR TKI and promising for E20ins EGFR mutation.

    • +

      P2.01-100 - Spectrum of EGFR Exon 20 Insertion Mutations and Co-Occurring Genetic Alterations in Patients with Non-Small-Cell Lung Cancer (ID 2538)

      10:15 - 18:15  |  Presenting Author(s): Gabriela Liliana Bravo Montenegro  |  Author(s): Misako Nagasaka, Patrick Chi-Chung Ma, abdul rafeh Naqash, Hirva Mamdani, Alexander Spira, Deepa S Subramaniam, Rebecca Feldman, Chul Kim

      • Abstract

      Background

      Epidermal growth factor receptor (EGFR) exon 20 insertion mutations are associated with a low response rate to approved EGFR tyrosine kinase inhibitors (EGFR-TKIs) and short progression-free survival. Pre-clinical studies have shown differences in the affinity of EGFR exon 20 insertion mutations for EGFR-TKIs, suggesting that the location of the insertion within the C-helix may play an important role in determining EGFR-TKI sensitivity. Several EGFR-TKIs designed to target EGFR exon 20 insertion mutations are in clinical development. Comprehensive genomic profiling has allowed for identification of co-occurring genomic alterations, which may help us identify additional pathways that may drive disease progression and drug resistance.

      Method

      Formalin-fixed paraffin-embedded (FFPE) samples from patients with non-small cell lung cancer (NSCLC) were profiled by targeted next-generation sequencing (NGS) using Caris Molecular Intelligence (Caris Life Sciences, Phoenix, AZ). Mutations and copy number variations (CNV) were assessed for each gene included in the NGS panel. Gene amplification (including low amplifications) was defined as gene copy number ≥ 4 and copy number loss as gene copy number < -1.4.

      Result

      Among the 1,556 patients with EGFR mutations, 104 (6.7%) patients were found to harbor an EGFR exon 20 insertion mutation. There were 70 (67.3%) females and 34 (32.7%) males with a mean age 62 (± 11.5 years). 61 (58.7%) samples came from primary lung sites and 43 samples (41.3%) came from metastatic sites. The main histological types were: adenocarcinoma 89 (85.5%), acinar adenocarcinoma 6 (5.7%), papillary adenocarcinoma 5 (4.8%), adenocarcinoma with bronchoalveolar features 1 (1%), squamous cell carcinoma 1 (1%) and carcinoma not otherwise specified 2 (2%). The most common exon 20 insertion mutation was A767_V769dup (25%), followed by S768_D770dup (13%), H773_V774insAH (5%) and H773dup (5%). The most common pathogenic mutations (including presumed pathogenic) included TP53 (51%), followed by CTNNB1 (6%), PIK3CA (4%), PTEN (3%), SMAD4 (3%), and CHEK2 (2%). Of the 104 cases, CNVs were available from 54 patients. Among these patients, commonly amplified genes included CDK4 (11%), EGFR (9%), MDM2 (9%), FOXA1 (7%), and HMGA2 (6%). Copy number loss was observed with CDKN2A (7%), CTNNB1 (2%), ATR (2%), BRCA2 (2%), and FANCL (2%).

      Conclusion

      The diverse spectrum of EGFR exon 20 insertion mutations shows molecular heterogeneity of this rare type of EGFR mutations. The presence of co-occurring genomic alterations that may promote tumor progression and drug resistance suggests that combination approaches may be necessary to overcome resistance to EGFR-TKI therapy in some patients with an EGFR exon 20 insertion mutation.

    • +

      P2.01-103 - Real-World Treatment Patterns and Survival in Non-Small Cell Lung Cancer Patients with EGFR Exon 20 Insertion Mutations (ID 1763)

      10:15 - 18:15  |  Presenting Author(s): Sai-Hong I Ou  |  Author(s): Maral Dersarkissian, Rachel Bhak, Huamao M Lin, Shuanglian Li, Mu Cheng, Angie Lax, Hui Huang, Mei Sheng Duh

      • Abstract
      • Slides

      Background

      Mutations in the epidermal growth factor receptor (EGFR) gene have been identified in 10-50% of patients with non-small cell lung cancer (NSCLC), and 2-10% are exon 20 insertion mutations. This study describes real-world characteristics, treatment patterns, and overall survival (OS) of NSCLC patients with EGFR exon 20 insertions.

      Method

      Flatiron Health electronic health record data from 1/2011-4/2018 were used for this retrospective study. Treatment-naïve (TN) and relapsed/refractory (RR) patients with advanced/metastatic NSCLC with EGFR exon 20 insertion mutation aged ≥18 years at treatment initiation were included. Patient characteristics were described, and Kaplan-Meier analyses were used to assess OS for TN and RR patients.

      Result

      There were 128 TN and 71 RR patients identified. Median age was 66.5 and 65.0 years for TN and RR patients, respectively, and over half were female (TN: 59.4%, RR: 53.5%). Among 83 TN and 47 RR patients with known ECOG score at advanced diagnosis, most had score 0-1 (TN: 56.3%, RR: 62.0%). Central nervous system metastases were observed in 35.2% of TN and 33.8% of RR patients. 45.3% of TN patients and 23.9% of RR patients received chemotherapy only. Approximately 20% of TN and RR patient were treated with EGFR TKI only. Only 6.3% of TN patients received any immuno-oncologic therapy (IO) or combination, while this was higher in RR patients (29.6%). Overall, median OS was low at 16.2 months for TN patients, and 12.5 months for RR patients. Treatment with any IO was associated with poor survival in TN (6.1 months) and RR (8.0 months) patients.

      table.png

      Conclusion

      OS of patients with EGFR exon 20 NSCLC remains poor. In TN patients, chemotherapy was the most common treatment, followed by EGFR TKIs. Treatment patterns were more diverse in RR patients. This study demonstrated unmet medical need for patients with NSCLC with EGFR exon 20 insertion mutation.

      IASLC Members: To view this content or have the option to purchase this event, click here to login.
      Conference Attendees & Access Code holders: Click here to enter your Access Code. Already entered your Access Code? Please login.