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Jun Zhao



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    FP14 - Targeted Therapy - Clinically Focused (ID 252)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP14.17 - Efficacy and Safety of Pralsetinib in Chinese Patients with Advanced RET Fusion+ Non-Small Cell Lung Cancer after Platinum-Based Chemotherapy (ID 2954)

      00:00 - 00:00  |  Author(s): Jun Zhao

      • Abstract

      Introduction

      RET fusions have been reported as oncogenic drivers in 1% to 2% of non-small cell lung cancer (NSCLC) patients. Pralsetinib is a highly potent and selective RET kinase inhibitor targeting oncogenic RET alterations. A global phase I/II ARROW study (NCT03037385) has demonstrated broad and durable antitumor activity of pralsetinib in a variety of advanced RET-altered solid tumors. Here we present the efficacy and safety results from the phase II NSCLC extension group that enrolled patients from China sites.

      Methods

      RET fusion+ Chinese NSCLC patients previously treated with platinum-based chemotherapy were enrolled and dosed with pralsetinib 400 mg QD. The primary objectives were to assess the objective response rate (ORR) by blinded independent central review (BICR) per RECIST v1.1 and safety profile in Chinese patients.

      Results

      From Aug to Dec 2019, a total of 37 patients were enrolled; most (94.6%) of the patients had ECOG PS of 1 and about half (48.6%) had received ≥3 prior systemic regimens. As of the data cut-off (22 May 2020), 28 patients remained on study treatment and 9 discontinued from pralsetinib (4 due to disease progression and 3 due to adverse events). The median treatment duration was 6.1 (range: 0.9-9.4) months. In 32 evaluable patients who had measurable disease at baseline per BICR, the ORR was 56.3% (95% CI: 37.7, 73.6) (1 complete response [CR] and 17 partial responses [PR]); in addition, 2 patients achieved PR pending confirmation. Clinical benefit rate (defined as the rate of confirmed CR or PR, or stable disease lasting ≥ 16 weeks from the first dose) was 81.3% (95% CI: 63.6, 92.8). Disease control rate was 96.9% (95% CI: 83.8, 99.9), and tumor regression was observed in all 13 patients with stable disease. The median time to response was 1.9 (range: 1.7-5.5) months. Median duration of response (DOR) was not reached; 6-month DOR rate was 83.1% (95% CI: 61.5, 100). All 37 patients experienced at least one treatment emergent adverse event (TEAE). The most frequently reported TEAEs were aspartate aminotransferase increased (83.8%), neutrophil count decreased (70.3%), anaemia (67.6%), white blood cell count decreased (56.8%), and hypertension (51.4%). Grade ≥ 3 TEAEs occurred in 25 (67.6%) patients, with the most common being neutrophil count decreased (24.3%), anaemia (24.3%), hypertension (16.2%), hypophosphataemia (13.5%), platelet count decreased (10.8%) and hypokalaemia (10.8%). There were no pralsetinib related AEs leading to death.

      Conclusion

      This is the first pivotal study to show that pralsetinib has deep and durable antitumor activity, and is well-tolerated in a cohort of Chinese patients with RET fusion+ NSCLC previously treated with platinum-based chemotherapy. The data are consistent with previously reported data from the global population in the ARROW trial. Overall, pralsetinib demonstrated a favorable benefit-risk profile, potentially offering a transformative medicine to Chinese RET-fusion driven advanced NSCLC patients.

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    JICC01 - Joint IASLC-CAALC-CSCO Session: The Truth and Myth of Oral Anti-VEGFR Inhibitors for Advance NSCLC (ID 276)

    • Event: WCLC 2020
    • Type: Workshop
    • Track: N.A.
    • Presentations: 1
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      JICC01.14 - Efficacy and Safety of Pralsetinib in Chinese Patients with Advanced RET Fusion+ Non-Small Cell Lung Cancer after Platinum-Based Chemotherapy (ID 4273)

      07:00 - 09:00  |  Author(s): Jun Zhao

      • Abstract

      Introduction
      RET fusions have been reported as oncogenic drivers in 1% to 2% of non-small cell lung cancer (NSCLC) patients. Pralsetinib is a highly potent and selective RET kinase inhibitor targeting oncogenic RET alterations. A global phase I/II ARROW study (NCT03037385) has demonstrated broad and durable antitumor activity of pralsetinib in a variety of advanced RET-altered solid tumors. Here we present the efficacy and safety results from the phase II NSCLC extension group that enrolled patients from China sites. Methods
      RET fusion+ Chinese NSCLC patients previously treated with platinum-based chemotherapy were enrolled and dosed with pralsetinib 400 mg QD. The primary objectives were to assess the objective response rate (ORR) by blinded independent central review (BICR) per RECIST v1.1 and safety profile in Chinese patients. Results

      From Aug to Dec 2019, a total of 37 patients were enrolled; most (94.6%) of the patients had ECOG PS of 1 and about half (48.6%) had received ≥3 prior systemic regimens. As of the data cut-off (22 May 2020), 28 patients remained on study treatment and 9 discontinued from pralsetinib (4 due to disease progression and 3 due to adverse events). The median treatment duration was 6.1 (range: 0.9-9.4) months. In 32 evaluable patients who had measurable disease at baseline per BICR, the ORR was 56.3% (95% CI: 37.7, 73.6) (1 complete response [CR] and 17 partial responses [PR]); in addition, 2 patients achieved PR pending confirmation. Clinical benefit rate (defined as the rate of confirmed CR or PR, or stable disease lasting ≥ 16 weeks from the first dose) was 81.3% (95% CI: 63.6, 92.8). Disease control rate was 96.9% (95% CI: 83.8, 99.9), and tumor regression was observed in all 13 patients with stable disease. The median time to response was 1.9 (range: 1.7-5.5) months. Median duration of response (DOR) was not reached; 6-month DOR rate was 83.1% (95% CI: 61.5, 100). All 37 patients experienced at least one treatment emergent adverse event (TEAE). The most frequently reported TEAEs were aspartate aminotransferase increased (83.8%), neutrophil count decreased (70.3%), anaemia (67.6%), white blood cell count decreased (56.8%), and hypertension (51.4%). Grade ≥ 3 TEAEs occurred in 25 (67.6%) patients, with the most common being neutrophil count decreased (24.3%), anaemia (24.3%), hypertension (16.2%), hypophosphataemia (13.5%), platelet count decreased (10.8%) and hypokalaemia (10.8%). There were no pralsetinib related AEs leading to death.

      Conclusion

      This is the first pivotal study to show that pralsetinib has deep and durable antitumor activity, and is well-tolerated in a cohort of Chinese patients with RET fusion+ NSCLC previously treated with platinum-based chemotherapy. The data are consistent with previously reported data from the global population in the ARROW trial. Overall, pralsetinib demonstrated a favorable benefit-risk profile, potentially offering a transformative medicine to Chinese RET-fusion driven advanced NSCLC patients.

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    P79 - Immunotherapy (Phase II/III Trials) - Immunotherapy Plus Chemotherapy (ID 256)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Immunotherapy (Phase II/III Trials)
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P79.02 - Updated OS and Time to Second Progression with First-Line Camrelizumab Plus Chemo vs Chemo for Advanced Non-Squamous NSCLC (ID 1732)

      00:00 - 00:00  |  Author(s): Jun Zhao

      • Abstract

      Introduction

      At the pre-specified interim analysis of the CameL phase 3 study, camrelizumab plus chemo (carboplatin + pemetrexed) as first-line therapy significantly improved the PFS compared with chemo alone and showed acceptable safety profile in patients with advanced non-squamous NSCLC without sensitizing EGFR and ALK alterations (2019 WCLC OA04.03). Herein, we provide an update on OS and PFS2 (time to second progression) based on long-term follow-up.

      Methods

      Eligible patients were randomized 1:1 to receive 4 to 6 cycles of chemo with (n=205) or without (n=207) camrelizumab, followed by pemetrexed with or without camrelizumab as maintenance therapy. Crossover to camrelizumab monotherapy was permitted for patients in the chemo alone group who had radiological disease progression. Data on post-study anticancer therapy and outcomes were collected. PFS2 was defined as time from randomization to disease progression after the first disease progression event or death, whichever occurred first. There was no multiplicity adjustment, and nominal one-sided P values are presented. ClinicalTrials.gov number: NCT03134872.

      Results

      At data cutoff on February 25, 2020, the median follow-up duration was 19.3 months (IQR 9.8−23.7). 35 (17.1%) patients in the camrelizumab plus chemo group and 18 (8.7%) in the chemo alone group were still receiving the assigned first-line study treatment. Camrelizumab plus chemo prolonged median overall survival, as compared with chemo alone (27.9 months [95% CI 21.9−not reached] vs 20.5 months [95% CI 15.9−24.­­4]; HR 0.73 [95% CI 0.55−0.96]; P=0.0117). Second-line or later therapy was received by 98 (47.8%) patients in the camrelizumab plus chemo group and 135 (65.2%) patients in the chemo alone group. Median PFS2 was 18.9 months (95% CI 15.7−21.2) vs 12.5 months (95% CI 10.6−15.6) in patients who received vs did not receive first-line camrelizumab (HR 0.66 [95% CI 0.52−0.84]; P=0.0004). Benefits in OS and PFS2 with camrelizumab plus chemo were also found in patients with PD-L1 TPS ≥1% (Table). The safety profile was consistent with the previous report at interim analysis.

      Table.

      OS

      PFS2

      No. events/No. patients

      HR (95% CI)

      P value

      No. events/No. patients

      HR (95% CI)

      P value

      Camrelizumab plus chemo

      Chemo alone

      Camrelizumab plus chemo

      Chemo alone

      All patients (n=412)

      44.9%

      54.6%

      0.73 (0.55−0.96)

      0.0117

      60.0%

      71.5%

      0.66 (0.52−0.84)

      0.0004

      Patients with PD-L1 TPS ≥1% (n=255)

      38.4%

      49.6%

      0.70 (0.48−1.02)

      0.0318

      53.6%

      67.5%

      0.64 (0.46−0.88)

      0.0027

      Conclusion

      Camrelizumab plus carboplatin and pemetrexed as first-line therapy showed long-term benefit in OS and PFS2 compared with chemo alone in Chinese patients with advanced non-squamous NSCLC without EGFR and ALK alterations, despite 48.3% of patients in the chemo alone group receiving subsequent immunotherapy. No new safety signal was observed. This combination represents a potential standard first-line therapy for these patients.

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    P83 - Immunotherapy (Phase II/III Trials) - Immunotherapy Plus Targeted Therapy (ID 260)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Immunotherapy (Phase II/III Trials)
    • Presentations: 2
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P83.01 - Updated Survival and Biomarker Analysis of Camrelizumab and Apatinib in Previously Treated pts of Advanced Non-Squamous NSCLC (ID 1657)

      00:00 - 00:00  |  Author(s): Jun Zhao

      • Abstract

      Introduction

      Our previous report showed that camrelizumab combination with apatinib have showed promising results in previously chemotherapy-treated patients with advanced non-squamous NSCLC. We further report the updated survival data and biomarkers analysis here.

      Methods

      1.jpgWe conduct a multi-center single-arm phase 1b/II study investigating the safety and efficacy of camrelizumab and apatinib in previously treated patients with advanced NSCLC. This study included phase 1b apatinib dose escalation phase and phase II population expansion cohort. The primary endpoints were safety and ORR respectively. Patients of non-squamous NSCLC who received apatinib 250 mg orally once daily in combination with camrelizumab 200 mg intravenously on day 1 every 2 weeks were included into this analysis (NCT03083041). 22C3 array was used for PD-L1 immunohistochemistry and OseqTM-pan cancer panel (including 636 genes and 1.95Mb) was used for the genomic alternation testing.

      Results

      Between March 21, 2017 and October 11, 2018, 105 patients were enrolled, 91patients had PD-L1 expression testing and 46 had sufficient tissue for NGS. As the cutoff of Aug 15, 2019, one had a confirmed complete response, 28 had confirmed partial response, and 48 had stable disease, ORR was 30.9% (29/94, 95% CI, 21.7-41.2%) in the efficacy-evaluable population (n=94). Median progression-free survival was 5.7 months (95% CI, 4.5–8.8) and median overall survival was 19.2 months (95% CI, 11.2-24.5) in all patients. PD-L1 expression was positive in 25(27.4%) patients, median TMB is 9 mutations/Mb, while STK11 and KEAP1 mutation were found in 7 and 10 patients respectively. Patients with PD-L1 TPS>1% and high TMB could not predict higher ORR (36.0% vs 22.7%, P = 0.20; 29.2% vs 36.4%, p=0.564, respectively) or longer PFS (median 6.8 vs 5.1 months, P = 0.61; 7.8 vs 8.0 months, P = 0.98). Notably, patients with STK11/KEAP1 mutation had a numerically higher ORR (42.9% vs 28.1%, P =0.327), longer PFS (median 9.4 vs 5.3, P = 0. 592) and statistically significantly longer OS (median NR vs NR, P = 0. 047) than those of wild type. The most common treatment-related adverse events of grade 3 or higher were hypertension (18 [17.1%]), palmar-plantar erythrodysesthesia syndrome (14 [13.3%]), and increased gamma-glutamyltransferase (10 [9.5%]).

      Conclusion

      Combined camrelizumab and apatinib had promising antitumor activity and acceptable safety in previously treated patients with advanced non-squamous NSCLC, especially in these with STK11 or KEAP1 mutation, phase III trial is ongoing for further validation (NCT04203485).

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      P83.03 - Efficacy of Camrelizumab (SHR-1210) Plus Apatinib in Advanced NSCLC with EGFR Mutation (ID 1864)

      00:00 - 00:00  |  Author(s): Jun Zhao

      • Abstract

      Introduction

      Treatment options are still limited for pts with advanced EGFR mutated NSCLC and resistant to EGFR-TKI. Here, we reported preliminary efficacy and safety of PD-1 camrelizumab (SHR-1210) plus apatinib in pts with EGFR mutation.

      Methods

      In this open-label, multi-center phase Ib/II study, pts aged 18-70 years, with EGFR mutation, and had disease progression on or after one line of platinum-based chemotherapy and at least one kind of EGFR-TKI were enrolled in dose escalation phase Ib and in dose expansion phase II. All pts received apatinib 250mg orally once daily plus camrelizumab 200mg every two weeks until disease progression or intolerable toxicity ( NCT03083041). Primary endpoint was objective response rate (ORR). Exploratory analyses of response and survival were conducted in pts classified by EGFR mutation types.

      Results

      Between Nov, 2017 and Jan, 2019, 40 NSCLC pts (3 in phase Ib and 37 in phase II) with EGFR mutation were enrolled. As the cutoff of December 15, 2019, the median follow-up was 10.8 months (range, 0.5-18.6). Four pts were still receiving treatment at the time of analysis. Among all 40 pts, 22 (55.0%) had EGFR 19 deletion (19del), 14 (35.0%) had L858R mutation, and 3 (7.5%) had EGFR 20 insertion (20ins). ORR was 20.0% (8/40, 95% CI, 9.1%-35.6%) and disease control rate (DCR) 62.5% (25/40, 95% CI, 45.8%-77.3%) in the whole population. Median duration of response was not reached (95% CI, 3.5-NR), median progression-free survival (mPFS) was 3.2 months (95% CI, 1.5-6.4m), and overall survival was not reached. Subgroup analysis showed that the ORR in pts with EGFR 20ins (n=3) or EGFR L858R(n=14) was higher than those with EGFR 19del (n=22) (33.3% vs. 21.4% vs. 13.6%, p=0.65). Similarly, longer mPFS was seen in pts with EGFR 20ins or L858R than in those with EGFR 19del (8.3m vs. 5.4m vs. 2.8m, p=0.94) . The most common treatment-related adverse events of grade 3 or higher were hypertension (7 [16.3%]), proteinuria (5 [11.6%]), palmar-plantar erythrodysesthesia syndrome (4 [9.3%]), and hypertriglyceridemia (3 [7.0%]).

      Table 1. Efficacy of camrelizumab and apatinib combination treatment in advanced NSCLC pts with EGFR mutation

      Pts

      ORR

      DCR

      mPFS (mos)

      mOS (mos)

      All pts

      40

      20.0%

      62.5%

      3.2

      NR

      EGFR 19del

      22

      13.6%

      59.1%

      2.8

      NR

      EGFR L858R

      14

      21.4%

      64.3%

      5.4

      NR

      EGFR 20ins

      3

      33.3%

      66.7%

      8.3

      NR

      Conclusion

      Camrelizumab plus apatinib showed a moderate benefit in pts with EGFR mutated NSCLC and showed better efficacy in pts with EGFR 20ins or L858R mutation sub-types, warrant further investigation.

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    P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P84.15 - Alectinib in Patients with ALK-Positive Advanced Non-Small Cell Lung Cancer as First-Line or Sequential Treatment in China (ID 2478)

      00:00 - 00:00  |  Author(s): Jun Zhao

      • Abstract

      Introduction

      Alectinib is a highly selective inhibitor of anaplastic lymphoma kinase (ALK) with superior systemic and central nervous system (CNS) efficacy. In ALEX study,alectinib yielded confirmed objective response rate(ORR) of 72.4%.The first-time real-world study aims to evaluate the efficacy and safety profile of alectinib in ALK-positive non-small cell lung cancer (NSCLC) Chinese patients.

      Methods

      A national retrospective cohort study of patients with ALK-positive NSCLC initiating alectinib(600 mg twice daily) was conducted in 7 centers in China between 01-Dec-2017 and 01-Sept- 2019.The last follow-up was to 31st December 2019.

      Results

      One hundred and two patients were enrolled.During a median follow-up of 10.6 months, an event of disease progression or death occurred in 21 of 102 patients (20.5%) .Patient Characteristics were shown in Table 1.

      For alectinib in the first-line setting, 39 patients were eligible for tumor evaluation.The ORR was 89.7%(35/39) and 2 patients had a complete response.Among 23 patients with measurable CNS lesions at baseline, a CNS response occurred in 22 of 23 patients (95.6%);4 patients had a complete CNS response.

      For alectinib in the sequential setting, 58 patients were eligible for tumor evaluation,of whom 37 patients received crizotinib as first-line therapy.The most common progression mode of crizotinib was CNS progression(24/37,64.9%).Fourty-four patients received alectinib as second-line treatment.The ORR was 75.9%(44/58) and 2 patients had a complete response. Among 51 patients with measurable CNS lesions, a CNS response occurred in 42 of 51 patients (82.4%);4 patients had a complete CNS response.

      Data of adverse events(AEs) were available in all patients.The most common AEs were increased blood bilirubin (23.5%),constipation(23.5%) and abnormal ALT and AST levels(22.5%).Other AEs that occurred in at least 10% of the patients included myalgia (12.7%), peripheral edema(11.8%) and rash(11.8%). Grade 3 AEs occurred in 8.8% of the patients.No grade 4 or 5 AEs were observed in this study. The most common grade 3 AEs were laboratory abnormalities(6/9,66.7%),of which was increased blood bilirubin leading to dose reduction to alectinib 300 mg twice daily.

      Table 1 Baseline Patient Characteristics

      Characteristics

      N%

      Age

      Medium (Range)

      51(24-81)

      Gender

      Male

      Female

      44(43.1%)

      58(56.9%)

      ECOG

      0-1

      ≥2

      82(80.3%)

      20(19.7%)

      Smoking history

      Yes

      No

      16(15.7%)

      86(84.3%)

      Histology

      Adenocarcinoma

      Squamous -cell carcinoma

      Large-cell carcinoma

      99(97.1%)

      2(2.0%)

      1(0.9%)

      Stage

      IIIB

      IV

      6(5.9%)

      96(94.1%)

      Metastasis site

      Brain

      Bone

      Liver

      44(43.1%)

      44(43.1%)

      15(14.7%)

      Alectinib treatment line

      First-line

      Second-line

      Beyond second-line

      41(40.2%)

      44(43.1%)

      17(16.7%)

      Previous Crizotinib treatment

      Yes

      No

      37(36.3%)

      65(63.7%)

      Previous chemotherapy

      Yes

      No

      24(23.5%)

      78(76.5%)

      Conclusion

      This study confirms the efficacy and safety of alectinib in real-world advanced ALK+ NSCLC in China, which is consistent with data reported in clinical trials.

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    P85 - Targeted Therapy - Clinically Focused - MET (ID 262)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P85.06 - Clinical and Genomic Features of Middle Intensity cMET Stain of Chinese Lung Cancer Patients (ID 1661)

      00:00 - 00:00  |  Author(s): Jun Zhao

      • Abstract

      Introduction

      Background:cMET overexpression has been identified as an oncogenic driver in Non-small cell lung cancer(NSCLC). About 25% NSCLC patients was detected cMET positive by immunohistochemistry(IHC) and has been studied for clinical and genomic features. Similarly, the clinical and genomic features of cMET negetive patients are need to be better understood.

      Methods

      Methods: Protein expression of cMET of 196 Chinese NSCLC patients by IHC was determined by measuring the intensity of the stain (0, 1+, 2+, 3+) and the percent staining (0-100%). We reviewed 132 of middle intensity cMET stain (cMET 1+/2+, negetive) with paired tumor-normal samples sequenced by 1021/59 gene panel.

      Results

      Results: In this study, 67.3% (132/196) were detected middle intensity cMET stain including 50.8% (67/132) cMET 2+. All of the patients were lung adenocarcinoma and the average age at diagnosis was 61.4 (range 33-80 years). 43.8% patients had a history of smoking. All of these characteristics were not significantly different between cMET 1+ and cMET 2+ groups. Differences was found in genomic. The common mutations were TP53(76/132), EGFR (74/132) and KRAS (23/132). 5 patients were found cMET activation mutations including 2 of cMET amplification and 3 of cMET mutation(Table 1). More non-synonymous mutation were found in cMET 2+ groups than cMET 1+ (media: 6 versus 5,p=0.02). Significantly higher number of copy numbers variations(CNV) was found in cMET 2+ groups (media: 2 versus 1, p=0.04,Fig 1). However, the gene mutations and actionable mutations were no differences in two groups except that MDM2 CNV mutation was higher in cMET 2+ groups(p=0.03).

      Table1. Genetic aberrations of MET.

      Patients Age Gender Smoking IHC of cMET NGS of cMET
      P1 61 Male NA cMET(2+) MET c.3028G>C
      P2 70 Femal NA cMET(1+) MET c.3028+3A>G
      P3 71 Male No cMET(2+) MET c.2888-19_2888-13delinsAAA
      P4 64 Male Yes cMET(1+) MET CNV
      P5 68 Femal No cMET(1+) MET CNV

      layout 2.png

      Conclusion

      Conclusion: Our data suggest that 3.8% middle intensity cMET stain patients had cMET activation which is a clearly therapeutic target to cMET inhibitors. cMET 2+ patients had more non-synonymous mutation and CNV than cMET 1+ patients which may be related to treatment and prognosis.

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    P89 - Targeted Therapy - Clinically Focused - Translational (ID 266)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P89.01 - Clinical and Genomic Features of EGFR-KDD/EGFR Rearrangements of Chinese Lung Cancer Patients (ID 2854)

      00:00 - 00:00  |  Author(s): Jun Zhao

      • Abstract

      Introduction

      Background:The most frequent epidermal growth factor receptor (EGFR) mutations of lung cancer include exon 19 in deletion and the exon 21 L858R mutation. And EGFR-tyrosine kinase inhibitor (TKI) as the standard first line treatment show good response to classical/sensitizing EGFR mutations. With the development of detection methods, some uncommon genomic mutation events such as exon 18-25 kinase domain duplications (KDD) and EGFR rearrangements are found. EGFR-KDD/EGFR rearrangements have been identified and implicated to be oncogenic in nonsmall cell lung cancers (NSCLCs). However, its prevalence and clinical contributions in lung cancer are largely unknown.

      Methods

      Methods: Here, we conducted our database record review of 10,560 lung cancer patients who underwent 1021-gene panel sequencing using next-generation sequencing (NGS). The panel contains EGFR exons and the introns involved in EGFR-KDD and EGFR rearrangements.

      Results

      Results: EGFR-KDD/EGFR rearrangements were identified in a total of 24 patients, which is approximately 0.23% of the total population reviewed, and also consisted of 0.39% (24/6188) of EGFR mutation-positive patients. A total of 30% of patients (8/24) were identified with EGFR-KDD which were the canonical EGFR-KDD duplication of exons 18–25, and 7 patients were adenocarcinoma and 1 patients was adenosquamous carcinoma. Importantly, none of the 8 patients had other coexisting driver mutations, highlighting the potential oncogenic role of this type of alteration. The others 16 patients were identified EGFR rearrangements, in which 2 patients were identified with the previously described EGFR rearrangements (EGFR-RAD51, EGFR-SEPT14), while the remaining 14 patients harbored not reported rearrangements. Different to the EGFR-KDD, 68.75% of patients (11/16) harbored other EGFR driver mutations including 7 of L858R, 3 of 19 deletions, and 1 of 20 insertions. As reported, we also found 56.25% of patients (9/16) harbored EGFR copy numbers variations. Most of the patients (12/16) were adenocarcinoma, and 4 of patients were NSCLC. Some reports had shown that several types of EGFR rearrangements were sensitive to EGFR-TKI therapists, but EGFR rearrangements were also found in 4 EGFR-TKI resistance patients. One of the patients harbored EGFR 19deletion and had 16 months therapy of osimertinib. Then, a VOPP1-EGFR was detected in the patients’ tissue after EGFR-TKI therapy, highlighting the potential resistance role of this type of alteration.

      Conclusion

      Conclusion: Our findings provide valuable insight into the prevalence of EGFR-KDD/EGFR rearrangements in Chinese lung cancer, and suggested that such rearrangements are clinically important genomic alterations.