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Ying Cheng
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JCSE 01 - Joint IASLC/CSCO/CAALC Session: Immunotherapy for Management of Lung Cancer: Ongoing Research from East and West (ID 630)
- Event: WCLC 2017
- Type: Joint Session IASLC/CSCO/CAALC
- Track: Immunology and Immunotherapy
- Presentations: 4
- Moderators:C. Bai, Fred R. Hirsch, Tony SK Mok, Yi-Long Wu
- Coordinates: 10/15/2017, 07:30 - 11:30, F203 (Annex Hall)
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JCSE 01.10 - The Main Treatment Failure Pattern for Completely Resected Stage II–IIIA (N1–N2) EGFR-Mutation Positive Lung Cancer (ID 10904)
10:05 - 10:20 | Author(s): Ying Cheng
- Abstract
- Presentation
Background:
ADJUVANT (CTONG 1104) is the first randomized trial shows significantly prolonged disease-free survival (DFS) in completely resected stage II-IIIA (N1-N2) epidermal growth factor receptor (EGFR)-mutation positive non-small-cell lung cancer (NSCLC) through adjuvant gefitinib compare with vinorelbine plus cisplatin (VP). Further we aim to analyze the treatment failure pattern in ADJUVANT study.
Method:
In the ADJUVANT trial, a total of 222 patients with completely resected stage N1–N2 EGFR-mutation positive NSCLC were randomized 1:1 into gefitinib group (250mg, QD, 24 months ) or vinorelbine (25mg/m[2] Day 1/Day 8) plus cisplatin (75mg/m[2] Day 1) group (every 3 weeks for 4 cycles) respectively. Any recurrence or metastases occurred during the follow-up period was defined as treatment failure. Recurrent pattern in both group were analyzed with follow-up data (until Mar 9[th] 2017) integrated.
Result:
At the Data cut-off date for the primary analysis of DFS, 124 progression events (55.9% maturity overall) had occurred; 114 patients had disease recurrence，10 patients died before disease recurrence. Analysed recurrent pattern include lung, brain, liver, bone adrenal gland, pleura, pericardium, spleen and regional lymph nodes metastasis. Even no significant differences were found, highest proportion of patients in both group(18.9% for VP and 26.1% for gefitinib, p=0.199) surfer brain metastasis with lung metastases being the second common recurrent site. Time to brain metastases showed no significantly difference between the two groups (not reach vs 40.8m, p>0.05). Among the 29 brain metastases patients with gefitinib, the brain metastases occurred in 17 patients during the gefitinib treament, and 12 patients relapse after the gefitnib termination. Figure 1
Conclusion:
Compared with other site metastases, lung, brain and regional lymph nodes metastases account for major proportion of recurrence in ADJUVANT study. (NCT01405079)
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JCSE 01.11 - A Multicenter, Non-Interventional Study on Real World EGFR Testing and in Patients with IIIB/IV NSCLC in Northern China (ID 10905)
10:20 - 10:35 | Presenting Author(s): Ying Cheng
- Abstract
- Presentation
Background:
EGFR mutation plays a dominant role in the precise treatment of non-small cell lung cancer (NSCLC), and EGFR-TKIs has been recommended for patients with positive EGFR-sensitive mutation as a standard regimen in clinical practice. In China, application of EGFR-TKIs without knowing EGFR mutation status has been a common phenomenon due to various reasons including the vast territory, uneven distribution of medical resources, differences level of testing technology and others. Therefore, we prospectively conducted a real-world investigation to understand the actual situation of EGFR testing in Northern China, and identify the underlying causes affecting EGFR detection, in order to provide references to improve the standardized treatment (NCT02620657).
Method:
The patients with IIIB/IV NSCLC who were firstly diagnosed or postoperative recurrence between 2014-1-1 and 2014-12-31 in 28 research centers of Northern China were analyzed. The primary endpoint was testing rate，the secondary endpoints were factors affecting EGFR testing, EGFR mutation status, detection methods and the survival outcomes of patients.
Result:
Among 2809 patients, 2250 (90.78%) were adenocarcinoma, 208 (7.40%) were squamous carcinoma, 51 (1.82%) were other pathologic types. Testing rate was 42.54% (1195/2809) and was significantly related to city level (first-tier cities vs. new first-tier cities vs. second-tier cities vs. third-tier and above cities : 69.04% vs. 38.08% vs. 34.05% vs. 14.11%, P < 0.001, smoking status (never smoking vs. ever smoking vs. smoking: 45.42% vs. 51.10% vs. 33.37%, P<0.001, ECOG PS (0 vs.1vs.2vs.≥3:47.93%vs. 44.48vs.34.89%vs.20.37%, P=0.011), pathological type (adenocarcinoma vs. squamous carcinoma: 44.94% vs.19.23%, P=0.003 and medical insurance situation (social basic medical insurance vs. new rural cooperative medical insurance vs. own expense: 44.98% vs. 36.49% vs. 29.55%, P=0.001. EGFR sensitive mutation rate was 46.44%, the most common subtype was 19Del (42.16%), followed by L858R(40.00%), Exon 20 insertions (1.62%) and other subtypes (16.20%). The most common methodology is ARMS (63.77%), the second common one is DNA sequencing (5.36%). The 1-year and 2-year survival rate in patients receiving EGFR testing was 73.6% and 51.9%, compared with 64.3% and 43.7% respectively in patients without EGFR testing.
Conclusion:
There were regional differences in EGFR testing rates among IIIB/IV NSCLC patients in Northern China. The intention of doctors and patients, medical insurance coverage and differences technical level are major factors affecting the testing rate of EGFR. Approaches should be taken to improve the situation, such as strengthening the training, expanding the coverage of medical insurance, and relying on commercial gene detection companies, and further standardize the molecularly pathological diagnosis and treatment of NSCLC.
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JCSE 01.24 - Detection of EGFR, ALK and Other Driver Oncogenes from Plasma cfDNA by Single Molecule Amplification and Re-sequencing Technology (cSMART) (ID 10920)
11:30 - 11:30 | Author(s): Ying Cheng
- Abstract
Background:
All patients with advanced stage NSCLC should have their EGFR and ALK mutation status known prior to initiation of first line therapy. Multiple plasma-based technologies such as ARMS and ddPCR are available for rapid detection of EGFR mutation, while only the more laborious Next Generation Sequencing (NGS) may cover EGFR, ALK and other uncommon mutations in a single blood test. cSMART is a novel NGS-based technology with rapid turnaround time that can detect EGFR, ALK and KRAS mutations plus others less common lung cancer specific driver oncogenes (BRAF, ROS-1, HER-2, PIK3CA, RET, MET14skipping).
Method:
Objectives of this study is to investigate the clinical application of cSMART on patients with advanced NSCLC. In cSMART assay, each cfDNA single allelic molecule is uniquely barcoded and universally amplified to make duplications. The amplified products are circularized and re-amplified with target-specific back-to-back primers. These DNA are then ligated with sequencing adapters and pair-end sequenced (>40,000x) with illumine sequencers. The original cfDNA molecules are reconstituted by multi-step bioinformatics pipeline for censor and correction. The final products are quantified for calculation of allele frequencies
Result:
Out of the 1664 samples tested, total of 1469 were of advanced stage NSCLC. We detected EGFR mutations in 758 (51.6%), ALK translocation in 34 (2.3%) and KRAS mutation in 78 (5.8%) patients. Among the patients with activating EGFR mutations, 301(39.7%) have exon 19 deletion and 279 (36.8%) have exon 21 point-mutation. Total of 6 (0.8%) patients with EGFR mutation have concurrent presence of ALK translocation. Incidence and mean allele frequency of the less common target mutation is summarized in Table. Median sample turnaround time is 7 days.Incidence (%) Median Mutation Allele frequency (%) BRAF 29 (1.97%) 0.08% ROS1 2 (0.14%) 0.77% HER-2 19 (1.29%) 0.20% PIK3CA 70 (4.77%) 0.17% RET 14 (0.95%) 0.57% MET14skipping 63 (4.29%) 0.08%
Conclusion:
cSMART is a novel plasma cfDNA-based technology that can detect the actionable target oncogenes for patients with advanced NSCLC. This is a sensitive method with capacity of detecting the uncommon targets at relatively low allele frequency.
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JCSE 01.25 - Detection of EGFR T790M Mutations by Four Testing Platforms in ctDNA from Chinese Patients with Advanced NSCLC (ID 10921)
11:30 - 11:30 | Author(s): Ying Cheng
- Abstract
Background:
Osimertinib is used to treat patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC). Detection of the T790M mutation in tissue samples may not be possible in some patients due to unfeasible or unsuccessful rebiopsies; detection in circulating cell-free tumor DNA (ctDNA) may represent a promising alternative. Here we evaluated four platforms to detect T790M using ctDNA in plasma from Chinese patients as part of the ADELOS study.
Method:
ADELOS is being conducted in China in 256 patients with advanced NSCLC, sensitizing mutations and progression on previous tyrosine kinase inhibitor. T790M was detected in plasma ctDNA by cobas® real-time polymerase chain reaction (PCR), super amplification refractory mutation system (Super-ARMS) PCR, QuantStudio3D digital PCR, and next-generation sequencing (NGS). T790M positive patients by any of the four platforms received osimertinib 80 mg/day orally. The relationship between T790M detection by each platform and objective response rate (ORR) was investigated. Concordance, sensitivity and specificity, and positive/negative predictive value between platforms were assessed. T790M mutation level in ctDNA was dynamically monitored every 6 weeks using digital PCR and NGS during osimertinib treatment, and its correlation with clinical outcome was evaluated. NGS also provided information about the heterogeneity of other genetic alterations in patients before osimertinib treatment.
Result:
Section will be completed in late-breaking abstract submission
Conclusion:
Section will be completed in late-breaking abstract submission
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MA 06 - Lung Cancer Biology I (ID 660)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
- Moderators:N. Motoi, Keith M Kerr
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 501
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MA 06.09 - Detection of EGFR T790M Mutations by Four Testing Platforms in ctDNA from Chinese Patients with Advanced NSCLC (ID 8615)
16:35 - 16:40 | Author(s): Ying Cheng
- Abstract
- Presentation
Background:
Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) targeting sensitizing mutations and T790M mutation, which causes ~60% of acquired resistance after first-line TKI treatment. T790M testing provides guidance for second-line treatment decisions. This study evaluated four T790M detection platforms using plasma circulating tumor DNA (ctDNA).
Method:
ADELOS is a multicentre, open-label, single-arm study (NCT 02997501) of Chinese patients with advanced non-small cell lung cancer (NSCLC) and progression on previous EGFR-TKI treatment. Plasma ctDNA testing for T790M was performed by Cobas[®] real-time polymerase chain reaction (PCR), super amplification refractory mutation system (Super-ARMS) PCR, capture-based next-generation sequencing (NGS, 168 gene panel), and QuantStudio3D digital PCR (3D dPCR). T790M-positive patients detected by these platforms received osimertinib 80 mg/day orally until progression. Matched tissue re-biopsy samples were also tested by Cobas[®] or NGS. The primary objectives were to evaluate concordance between the Cobas[®] test and the other three platforms and to assess the efficacy of osimertinib in ctDNA T790M-positive patients.
Result:
Of 256 patients enrolled, 181 were ctDNA T790M-positive, among which 167 received osimertinib monotherapy. T790M plasma positive rate was from 37.4% to 63.5% (Cobas[®]< Super-ARMSCobas[®] PCR n=254 Super-ARMS PCR n=256 NGS n=256 3D dPCR n=255 T790M detected, n (%) 95 (37.4) 108 (42.2) 138 (53.9) 162 (63.5) Comparison vs Cobas plasma test (n=254) Concordance %, (95% CI) -- 91.3 (87.2, 94.5) 82.7 (77.5, 87.1) 66.8 (60.6, 72.6) Sensitivity %, (95% CI) -- 94.7 (88.1, 98.3) 98.9 (94.3, 100.0) 90.5 (82.8, 95.6) Specificity %, (95% CI) -- 89.3 (83.4, 93.6) 73.0 (65.3, 79.7) 52.5 (44.4, 60.5) Comparison vs Tissue (n=73) Concordance %, (95% CI) 67.1 (55.1, 77.7) 64.4 (52.3, 75.3) 69.9 (58.0, 80.1) 61.6 (49.5, 72.8) Sensitivity %, (95% CI) 57.1 (42.2, 71.2) 61.2 (46.2, 74.8) 71.4 (56.7, 83.4) 69.4 (54.6, 81.7) Specificity %, (95% CI) 87.5 (67.6, 97.3) 70.8 (48.9, 87.4) 66.7 (44.7, 84.4) 45.8 (25.6, 67.2)
Conclusion:
Super-ARMS showed highest concordance and NGS showed highest sensitivity compared with Cobas® plasma T790M testing. Concordance and specificity of 3D dPCR was lower using other ctDNA tests or tissue as reference. Subsequent osimertinib treatment in these patients will justify the effectiveness of T790M testing by different technologies.
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MA 11 - Emerging Diagnostic/Biomarkers in NSCLC (ID 668)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:M.I. Abdul Wahid, Martin Reck
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 313 + 314
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MA 11.03 - Gefitinib as First-Line Treatment of Plasma CtDNA EGFR Mutation-Positive NSCLC Detected by DdPCR: BENEFIT Study (CTONG1405) (ID 9278)
11:10 - 11:15 | Author(s): Ying Cheng
- Abstract
- Presentation
Background:
EGFR mutations in plasma circulating free tumor-derived DNA (ctDNA) as a predictor of EGFR TKI efficacy in patients with NSCLC requires validation in prospective studies. The large, prospective Phase II, single-arm, multicenter BENEFIT study (CTONG1405; NCT02282267) validated the efficacy of first-line gefitinib in EGFR mutation-positive NSCLC detected in plasma ctDNA using droplet digital PCR (ddPCR).
Method:
Patients with stage IV lung adenocarcinoma and plasma ctDNA EGFR-sensitizing mutations (exon 19 del or exon 21 L858R; by ddPCR) received first-line gefitinib (250 mg once-daily) until progressive disease (PD). Blood samples were collected every 8 weeks for dynamic EGFR analysis until PD. Primary endpoint was ORR. Secondary endpoints included PFS, DCR (Week 8), and analysis of baseline ctDNA samples by next-generation sequencing (NGS).
Result:
From December 2014-January 2016, 426 patients from 15 Chinese centers were screened: 391 had matched tissue and blood samples; 188 had ctDNA EGFR mutation-positive NSCLC and received gefitinib; and 183 had ≥1 post-baseline tumor assessment and plasma samples every 8 weeks until PD. At data cutoff (January 31, 2017), 152 patients had progressed. ORR was 72.1% (95% CI 65.0%,78.5%); DCR (Week 8) was 92.3% (95% CI 87.5%,95.8%); and median PFS was 9.5 months (95% CI 9.07,11.04). PFS was significantly shorter in the subgroup with baseline ctDNA de novo T790M mutations (5.0%, n=9) versus the EGFR-sensitizing mutations subgroup (5.6 vs 9.6 months, HR=2.60; 95% CI 1.32,5.12, p=0.004). In patients with Week 8 on-treatment plasma samples (n=167), the subgroup who showed EGFR mutation clearance in ctDNA by ddPCR (88%, 147/167) had longer PFS compared with those who did not (11.0 vs 2.1 months, HR=7.28; 95% CI 4.35,12.18, p<0.0001). The median time to emergence of acquired T790M mutation in plasma was 7.6 months. The T790M-positive rate increased from Week 24 (15.7%) to Week 48 (32.6%), with a corresponding increase in PD rate (24.7% at Week 24, 56.9% at Week 48). Among 180 patients with baseline NGS data, 21 (11.7%) harbored aberrations in additional oncogenic drivers (MET, ERBB2, KRAS, BRAF, RET, or ROS1) and tumor suppressors (TP53, RB1, and PTEN). This subgroup had worse PFS versus those with EGFR-sensitizing mutations alone (3.9 vs 13.0 months, HR=2.83; 95% CI 1.65,4.87, p=0.00016).
Conclusion:
The BENEFIT study prospectively demonstrated that ctDNA-based EGFR mutation detection can be used to select patients for treatment with first-line gefitinib. Dynamic alterations in EGFR mutations could be used to predict efficacy and disease progression, ahead of radiological results.
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OA 05 - Next Generation TKI (ID 657)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:James Chih-Hsin Yang, Fiona Blackhall
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 301 + 302
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OA 05.01 - First-Line Dacomitinib versus Gefitinib in Advanced Non-Small-Cell Lung Cancer with EGFR Mutation Subgroups (ID 8555)
15:45 - 15:55 | Author(s): Ying Cheng
- Abstract
- Presentation
Background:
The ARCHER 1050 study (NCT01774721) demonstrated benefits of dacomitinib compared with gefitinib as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) and EGFR-activating mutation. Here, we present the results of a prospective subgroup analysis by EGFR mutation subtype.
Method:
In this ongoing phase 3, open-label study, eligible patients with newly diagnosed stage IIIb/IV or recurrent NSCLC and EGFR-activating mutation (exon 19 deletion or L858R mutation ± T790M mutation) with an Eastern Cooperative Oncology Group performance status of 0–1 were randomized (1:1) to receive dacomitinib or gefitinib, stratified by race and EGFR mutation subtype. The primary endpoint was progression-free survival (PFS) by blinded independent radiologic central (IRC) review. Secondary endpoints included overall survival and objective response rate (ORR), as determined by IRC and investigators’ assessments.
Result:
A total of 452 patients were randomized (dacomitinib, n=227; gefitinib, n=225). Among the dacomitinib and gefitinib arms, respectively, 134 (59%) and 133 (59%) had exon 19 deletions and 93 (41%) and 92 (41%) had L858R mutations. The Table shows PFS, ORR, and duration of response by EGFR mutation per IRC. Results based on investigators’ assessments were consistent with those based on IRC review. Overall survival data are immature.Exon 19 Deletion L858R Mutation Dacomitinib (n=134) Gefitinib (n=133) Dacomitinib (n=93) Gefitinib(n=92) PFS per IRC Median, months (95% CI) 16.5 (11.3–18.4) 9.2 (9.1–11.0) 12.3 (9.2–16.0) 9.8 (7.6–11.1) Hazard ratio (95% CI) 1-sided P value 0.551 (0.408–0.745) <0.0001 0.626 (0.444–0.883) 0.0034 ORR per IRC CR, n (%) 7 (5.2) 3 (2.3) 5 (5.4) 1 (1.1) PR, n (%) 95 (70.9) 90 (67.7) 63 (67.7) 67 (72.8) ORR (CR + PR), n (%) (95% CI) 102 (76.1) (68.0–83.1) 93 (69.9) (61.4–77.6) 68 (73.1) (62.9–81.8) 68 (73.9) (63.7–82.5) 1-sided P value 0.1143 0.5395 DoR in responders per IRC Median, months (95% CI) 15.6 (13.1–19.6) 8.3 (7.9–10.1) 13.7 (9.2–17.4) 7.5 (6.5–10.2) Hazard ratio (95% CI) 1-sided P value 0.454 (0.319–0.645) <0.0001 0.403 (0.267–0.607) <0.0001 CI, confidence interval; CR, complete response; DoR, duration of response; PR, partial response.
Conclusion:
By IRC and investigators’ assessments, PFS with dacomitinib was superior to that with gefitinib in patients with either EGFR mutation. Despite a similar ORR among the treatment and EGFR mutation subgroups, duration of response was longer with dacomitinib for both mutations.
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-032 - Detection of EGFR, ALK and Other Driver Oncogenes from Plasma cfDNA by Single Molecule Amplification and Re-sequencing Technology (cSMART) (ID 8603)
09:30 - 09:30 | Author(s): Ying Cheng
- Abstract
Background:
All patients with advanced stage NSCLC should have their EGFR and ALK mutation status known prior to initiation of first line therapy. Multiple plasma-based technologies such as ARMS and ddPCR are available for rapid detection of EGFR mutation, while only the more laborious Next Generation Sequencing (NGS) may cover EGFR, ALK and other uncommon mutations in a single blood test. cSMART is a novel NGS-based technology with rapid turnaround time that can detect EGFR, ALK and KRAS mutations plus others less common lung cancer specific driver oncogenes (BRAF, ROS-1, HER-2, PIK3CA, RET, MET14skipping).
Method:
Objectives of this study is to investigate the clinical application of cSMART on patients with advanced NSCLC. In cSMART assay, each cfDNA single allelic molecule is uniquely barcoded and universally amplified to make duplications. The amplified products are circularized and re-amplified with target-specific back-to-back primers. These DNA are then ligated with sequencing adapters and pair-end sequenced (>40,000x) with illumine sequencers. The original cfDNA molecules are reconstituted by multi-step bioinformatics pipeline for censor and correction. The final products are quantified for calculation of allele frequencies
Result:
Out of the 1664 samples tested, total of 1469 were of advanced stage NSCLC. We detected EGFR mutations in 758 (51.6%), ALK translocation in 34 (2.3%) and KRAS mutation in 78 (5.8%) patients. Among the patients with activating EGFR mutations, 301(39.7%) have exon 19 deletion and 279 (36.8%) have exon 21 point-mutation. Total of 6 (0.8%) patients with EGFR mutation have concurrent presence of ALK translocation. Incidence and mean allele frequency of the less common target mutation is summarized in Table. Median sample turnaround time is 7 days.Incidence (%) Median Mutation Allele frequency (%) BRAF 29 (1.97%) 0.08% ROS1 2 (0.14%) 0.77% HER-2 19 (1.29%) 0.20% PIK3CA 70 (4.77%) 0.17% RET 14 (0.95%) 0.57% MET14skipping 63 (4.29%) 0.08%
Conclusion:
cSMART is a novel plasma cfDNA-based technology that can detect the actionable target oncogenes for patients with advanced NSCLC. This is a sensitive method with capacity of detecting the uncommon targets at relatively low allele frequency.
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P1.04 - Clinical Design, Statistics and Clinical Trials (ID 690)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.04-010 - CheckMate 870: An Open-label Safety Study of Nivolumab in Previously Treated Patients With Non-Small Cell Lung Cancer in Asia (ID 8231)
09:30 - 09:30 | Author(s): Ying Cheng
- Abstract
Background:
Programmed death-1 (PD-1) is an immune checkpoint receptor that attenuates T-cell activation by binding to its ligands, PD-L1 and PD-L2, which are expressed on tumor cells. Nivolumab, an anti–PD-1 antibody, showed durable antitumor activity and a favorable safety profile compared with docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC) in 2 global phase 3 studies (CheckMate 017 and CheckMate 057). Data from these trials led to the approval of weight-based nivolumab 3 mg/kg administered as a 60-minute infusion every 2 weeks (Q2W) in previously treated patients with NSCLC. Data from exposure-response simulations indicated that flat-dose nivolumab 240 mg Q2W has comparable pharmacokinetic, safety, and efficacy profiles to the weight-based dose, and data from CheckMate 153 demonstrated that nivolumab 3 mg/kg can be safely infused over 30 minutes. CheckMate 078 is an ongoing phase 3 registrational trial evaluating second-line nivolumab 3 mg/kg as 60-minute infusions Q2W versus docetaxel in patients with advanced NSCLC in a predominantly Chinese population. CheckMate 078 excludes patients with hepatitis B virus (HBV) infection, which represent a clinically relevant subgroup of patients in Asia; approximately 15% of patients with lung cancer in China are seropositive for HBV surface antigens. CheckMate 870 is an open-label, single-arm phase 3b study evaluating the safety and tolerability of flat-dose nivolumab 240 mg infused over 30 minutes Q2W in Asian patients with advanced or metastatic NSCLC, with or without HBV infection.
Method:
Approximately 400 patients in Asia with advanced or metastatic NSCLC and disease progression during or after 1 prior systemic platinum-based therapy will be enrolled; those with EGFR mutations (maximum of 40 patients) or ALK translocations should have received 2 prior systemic treatments including a tyrosine kinase inhibitor and chemotherapy. Nivolumab will be administered 240 mg over 30 minutes Q2W until disease progression or unacceptable toxicity, for a maximum of 24 months. Nivolumab may be reinitiated for subsequent disease progression and administered for up to 1 additional year. The primary objective is to evaluate the safety and tolerability of nivolumab in non–HBV-infected patients with NSCLC. The secondary objective is to assess safety and tolerability in all patients and in HBV-infected patients. Exploratory objectives include efficacy, patient-reported outcomes, health care resource utilization and direct medical costs, biomarker characterization in all patients, and viral load change and HBV reactivation rate in HBV-infected patients.
Result:
Section not applicable
Conclusion:
Section not applicable
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P1.15 - SCLC/Neuroendocrine Tumors (ID 701)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.15-016 - The Study of Population Pharmacokinetics and Individualized Dosage of Lobaplatin-Based Regimens in Elderly Patients with Small Cell Lung Cancer (ID 9766)
09:30 - 09:30 | Presenting Author(s): Ying Cheng
- Abstract
Background:
Elderly patients with SCLC have limited treatment options and poor survival. Lobaplatin(LBP) is a representative of the third-generation platinum compound, which has showed significant efficacy and favorable toxicity for SCLC. Therefore, we adopt population pharmacokinetic methods to explore the pharmacokinetics and its correlation with adverse reactions, and to make individualized dosing regimens of lobaplatin for elderly SCLC patients.(ChiCTR-OPN-15006057)
Method:
SCLC patients aged≥65 years and creatinine clearance(Ccr) ≥60ml/min were divided into two arms, receiving four cycles of lobaplatin regimens according to Ccr. LBP was administrated at dose of 30mg/m[2 ]in Arm A(Ccr≥80ml/min) or 20mg/m[2] in Arm B(60ml/min≤Ccr＜80ml/min). Four blood samples were randomized collected from each patient in the first cycle. For the subsequent cycles, only one blood sample were collected. The primary endpoint was plasma concentrations at different time points after administration of LBP. The secondary endpoints were PFS, OS, ORR, DCR and safety.
Result:
Between January 2014 and July 2016, 100 patients(30 with limited stage and 70 with extensive stage disease) were enrolled into the study at 7 institutions in China. There were 51 patients in Arm A and 49 patients in Arm B. The median PFS and OS for Arm A and B were 155 days vs.170 days, 306 days vs. 272 days, respectively. The ORR and DCR were 50% vs. 51.22%, 88.64% vs. 90.24% respectively. Grade III/IV AEs incidence of Arm A and B were 60.8% vs. 51.0%. In terms of population pharmacokinetic, we can get the following conclusions by computer simulation that if the total doses of LBP are fixed, the exposure levels of lobaplatin in the body have great differences when the body surface areas(BSA) are different. If administrated according to the BSA, the AUC differences of individual with different BSA are little, and there is only about 8% AUC differences between the two arms. As administrated in accordance with the protocol, the AUC of Arm B is about 39% lower than that of Arm A. If dose of LBP in Arm B was increased from 20 mg/m2 to 27 mg/m2, the AUC difference between the two groups was only 3%.
Conclusion:
When Ccr≥60 ml/min, it’s necessary to administration on the basis of BSA. It’s reliable and safe to use LBP-based regimens to treat elderly patients with SCLC. Lobaplatin may offer an alternative choice for Chinese elderly patients with advanced SCLC.
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-047 - The Main Treatment Failure Pattern for Completely Resected Stage II–IIIA (N1–N2) EGFR-Mutation Positive Lung Cancer (ID 9743)
09:30 - 09:30 | Author(s): Ying Cheng
- Abstract
Background:
ADJUVANT (CTONG 1104) is the first randomized trial shows significantly prolonged disease-free survival (DFS) in completely resected stage II-IIIA (N1-N2) epidermal growth factor receptor (EGFR)-mutation positive non-small-cell lung cancer (NSCLC) through adjuvant gefitinib compare with vinorelbine plus cisplatin (VP). Further we aim to analyze the treatment failure pattern in ADJUVANT study.
Method:
In the ADJUVANT trial, a total of 222 patients with completely resected stage N1–N2 EGFR-mutation positive NSCLC were randomized 1:1 into gefitinib group (250mg, QD, 24 months ) or vinorelbine (25mg/m[2] Day 1/Day 8) plus cisplatin (75mg/m[2] Day 1) group (every 3 weeks for 4 cycles) respectively. Any recurrence or metastases occurred during the follow-up period was defined as treatment failure. Recurrent pattern in both group were analyzed with follow-up data (until Mar 9[th] 2017) integrated.
Result:
At the Data cut-off date for the primary analysis of DFS, 124 progression events (55.9% maturity overall) had occurred; 114 patients had disease recurrence，10 patients died before disease recurrence. Analysed recurrent pattern include lung, brain, liver, bone adrenal gland, pleura, pericardium, spleen and regional lymph nodes metastasis. Even no significant differences were found, highest proportion of patients in both group(18.9% for VP and 26.1% for gefitinib, p=0.199) surfer brain metastasis with lung metastases being the second common recurrent site. Time to brain metastases showed no significantly difference between the two groups (not reach vs 40.8m, p>0.05). Among the 29 brain metastases patients with gefitinib, the brain metastases occurred in 17 patients during the gefitinib treament, and 12 patients relapse after the gefitnib termination. Figure 1
Conclusion:
Compared with other site metastases, lung, brain and regional lymph nodes metastases account for major proportion of recurrence in ADJUVANT study. (NCT01405079)
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 4
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-012 - Symptom Impact of First-Line Dacomitinib versus Gefitinib in EGFR-Positive NSCLC: Results from a Randomized Phase 3 Study (ID 8569)
09:30 - 09:30 | Author(s): Ying Cheng
- Abstract
Background:
Patients with non-small-cell lung cancer (NSCLC) experience high disease burden due to many cancer-related symptoms (eg, cough, dyspnea, pain, and fatigue). Decreasing tumor burden may reduce/delay symptoms and favorably impact global health-related quality of life (HRQoL). Dacomitinib is an irreversible, small-molecule inhibitor of EGFR/HER-1, HER-2, and HER-4 tyrosine kinases. In a global, multicenter, randomized, open-label phase 3 study (NCT01774721) for first-line treatment of NSCLC, dacomitinib improved the primary objective of progression-free survival per independent radiologic review (median, 14.7 vs 9.2 months; hazard ratio, 0.59; 95% confidence interval [CI], 0.47–0.74; P<0.0001) over gefitinib. Median duration of treatment was longer with dacomitinib than with gefitinib (67 vs 52 weeks, respectively).[1] A secondary objective was to explore HRQoL. Here, we report the impact of dacomitinib and gefitinib treatment on core lung cancer symptoms.
Method:
Patients were randomized 1:1 to receive oral dacomitinib (45 mg) or gefitinib (250 mg) once daily. Disease-related symptoms were measured using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire–Core 30 (QLQ-C30) and Lung Cancer 13 (QLQ-LC13). Scores were summarized by the mean and 95% CI for each group and plotted over 30 cycles and at the end of treatment; the number of cycles (n=30) chosen for this analysis was not prespecified. Mean changes from baseline (cycle 1, day 1 [C1D1]) were reported for each group.
Result:
Between 9-May-2013 and 20-March-2015, 452 patients were randomly assigned to dacomitinib (n=227) or gefitinib (n=225). Baseline scores were similar between treatment arms. On-study completion rates were high, with >90% of patients answering all questions for most treatment cycles. Statistically significant improvements from baseline (95% CI excludes 0; no adjustment for multiplicity) for most cycles were seen in fatigue, pain, dyspnea, and cough in both arms. Improvements were reported as early as C1D8. Clinically meaningful improvements (≥10 points score change) were recorded for pain in chest (23/30 cycles) and cough (28/30 cycles) with dacomitinib and for cough (22/30 cycles) with gefitinib; hence, improvements appear to be more frequent with dacomitinib. Symptom burden at end of treatment was generally higher than during treatment. As treatment duration was longer with dacomitinib, key lung cancer symptom improvements were seen for a longer time in patients treated with dacomitinib.
Conclusion:
Dacomitinib, along with gefitinib, demonstrated favorable clinical benefit and improvements in key NSCLC symptoms. These findings are important when considering choice of therapy. Reference 1. Mok T, et al. J Clin Oncol. 2017;35(Suppl):abstract LBA9007.
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P3.01-021 - A Multicenter, Non-Interventional Study on Real World EGFR Testing and in Patients with IIIB/IV NSCLC in Northern China (ID 8897)
09:30 - 09:30 | Presenting Author(s): Ying Cheng
- Abstract
Background:
EGFR mutation plays a dominant role in the precise treatment of non-small cell lung cancer (NSCLC), and EGFR-TKIs has been recommended for patients with positive EGFR-sensitive mutation as a standard regimen in clinical practice. In China, application of EGFR-TKIs without knowing EGFR mutation status has been a common phenomenon due to various reasons including the vast territory, uneven distribution of medical resources, differences level of testing technology and others. Therefore, we prospectively conducted a real-world investigation to understand the actual situation of EGFR testing in Northern China, and identify the underlying causes affecting EGFR detection, in order to provide references to improve the standardized treatment.( NCT02620657)
Method:
The patients with IIIB/IV NSCLC who were firstly diagnosed or postoperative recurrence between 2014-1-1 and 2014-12-31 in 28 research centers of Northern China were analyzed. The primary endpoint was testing rate，the secondary endpoints were factors affecting EGFR testing, EGFR mutation status, detection methods and the survival outcomes of patients.
Result:
Among 2809 patients, 2250(90.78%) were adenocarcinoma, 208(7.40%) were squamous carcinoma, 51(1.82%) were other pathologic types. Testing rate was 42.54%(1195/2809) and was significantly related to city level (first-tier cities vs. new first-tier cities vs. second-tier cities vs. third-tier and above cities : 69.04% vs. 38.08% vs. 34.05% vs. 14.11%, P < 0.001), smoking status (never smoking vs. ever smoking vs. smoking: 45.42% vs. 51.10% vs. 33.37%, P<0.001), ECOG PS(0 vs.1vs.2vs.≥3:47.93%vs. 44.48vs.34.89%vs.20.37%, P=0.011), pathological type (adenocarcinoma vs. squamous carcinoma: 44.94% vs.19.23%, P=0.003) and medical insurance situation (social basic medical insurance vs. new rural cooperative medical insurance vs. own expense: 44.98% vs. 36.49% vs. 29.55%, P=0.001). EGFR sensitive mutation rate was 46.44%, the most common subtype was 19Del(42.16%), followed by L858R(40.00%), Exon 20 insertions(1.62%) and other subtypes(16.20%). The most common methodology is ARMS(63.77%), the second common one is DNA sequencing(5.36%). The 1-year and 2-year survival rate in patients receiving EGFR testing was 73.6%and 51.9%, compared with 64.3% and 43.7% respectively in patients without EGFR testing.
Conclusion:
There were regional differences in EGFR testing rates among IIIB/IV NSCLC patients in Northern China. The intention of doctors and patients, medical insurance coverage and differences technical level are major factors affecting the testing rate of EGFR. Approaches should be taken to improve the situation, such as strengthening the training, expanding the coverage of medical insurance, and relying on commercial gene detection companies, and further standardize the molecularly pathological diagnosis and treatment of NSCLC.
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P3.01-036 - A Phase IIIb Open-Label, Single-Arm Study of Afatinib in EGFR TKI-Naïve Patients with EGFRm+ NSCLC: An Interim Analysis (ID 9251)
09:30 - 09:30 | Author(s): Ying Cheng
- Abstract
Background:
In the Phase III LUX-Lung (LL) 3 and LL6 trials, first-line afatinib significantly improved PFS vs platinum-doublet chemotherapy in patients with EGFRm+ NSCLC (independent review; LL3: 11.1 vs 6.9 months, HR=0.58; p=0.001; LL6: 11.0 vs 5.6 months, HR=0.28; p<0.0001). In the Phase IIb LL7 trial, afatinib significantly improved PFS and TTF vs gefitinib in patients with EGFRm+ NSCLC harboring common EGFR mutations (PFS, independent review: 11.0 vs 10.9 months, HR=0.73; p=0.017; TTF: 13.7 vs 11.5 months, HR=0.73, p=0.0073). Here we report interim analysis results of a large Phase IIIb study of afatinib in a broad population of EGFR TKI-naïve patients with EGFRm+ NSCLC.
Method:
In this Phase IIIb trial with a similar setting to ‘real-world’ practice, EGFR TKI-naïve patients with locally advanced/metastatic EGFRm+ NSCLC were recruited from centers in China, Hong Kong, India, Singapore and Taiwan and received afatinib 40mg/day until investigator-assessed progression or lack of tolerability. Primary endpoint: number of patients with serious adverse events (SAEs). Secondary endpoints included: number of patients with afatinib-related AEs; time to symptomatic progression (TTSP). Other assessments included PFS (investigator review).
Result:
At data cut-off (13 Feb 2017) 479 patients were treated with afatinib (median age: 59.0 years; female: 52.4%; common [(Del19 and/or L858R) with or without uncommon]/uncommon only EGFR mutations: 86.0%/14.0%; ECOG PS 0/1: 19.8%/78.1%; brain metastases: 19.2%; 0/1/≥2 lines of prior chemotherapy: 59.7%/30.1%/10.2%. 24.8% of patients required dose reductions to 30mg; 6.1% had further reductions to 20mg. Median (range) treatment time was 9.7 months (0.2–38.6). SAEs were reported in 115 (24.0%) patients and afatinib-related SAEs in 29 (6.1%) patients. Grade ≥3 afatinib-related AEs occurred in 122 (25.5%) patients; diarrhea (n=50; 10.4%) and rash/acne (n=38; 7.9%) were the most common (≥5%). 18 (3.8%) patients discontinued treatment due to afatinib-related AEs. Median TTSP (15.3 months [95% CI: 13.4–17.5]) was 3 months longer than PFS (12.1 months [10.8–13.7]), suggesting afatinib may be continued beyond progression, and both were longer in patients with common (with/without uncommon) vs uncommon only EGFR mutations (PFS: 12.6 vs 9.1; TTSP: 15.8 vs 10.0 months).
Conclusion:
The safety data of afatinib from this interim analysis of a large-scale population of EGFR TKI-naïve EGFRm+ NSCLC patients are consistent with LL3/6/7 and confirm that most afatinib-related AEs are manageable and result in few treatment discontinuations. Afatinib also demonstrated encouraging efficacy in patients with common and uncommon EGFR mutations. Data from larger patient populations will be evaluated in further analyses of this trial.
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P3.01-087 - Impact Factor Analysis for Efficacy and Prognosis of Anlotinib in NSCLC as Third-Line Treatment: Data from Trial ALTER 0303 (ID 9129)
09:30 - 09:30 | Author(s): Ying Cheng
- Abstract
Background:
Anlotinib hydrochloride is a novel TKI targeting the VEGFR, FGFR, PDGFR and c-Kit. With the capability of inhibiting the tumor angiogenesis and tumor cell itself, anlotinib had showed significantly improvement in OS (9.63 vs. 6.30 months, HR=0.68, 95%CI 0.54-0.87, p=0.0018) and PFS (5.37 vs. 1.40 months, HR=0.26, 95%CI 0.21-0.33, p<0.0001) in ALTER 0303 study for refractory cancer, a randomized, double-blind, placebo-controlled Phase Ⅲ trial in China. Here, we report the main impact factors affecting the efficacy and prognosis of anlotinib based on the data from ALTER0303 to elucidate the most benefit population.
Method:
Analyzed data were collected from 294 patients that were enrolled in ALTER0303 trial and received anlotinib treatment between 4[th] March 2015 and 15[th] August 2016. The statistical analysis was conducted using SPSS19.0 software, in which the measuring and enumeration materials were described with Mean±SD and frequency/percentage respectively, Kaplan-Meier method was used for survival curves in survival analysis. Independent impact factors of OS and PFS were identified by univariate and multivariate analysis in Cox proportional hazards regression model (Significant level, α=0.05).
Result:
Several factors were discovered to be associated with the efficacy of Anlotinib treatment. The impact factors were presented in Tab1.Tab1. Impact factors for PFS and OS analyzed by Cox proportional hazards regression model Independent risk factor Independent protective factor PFS Ratio of granulocytes to lymphocytes at PD (HR=1.07, 95%CI 1.041-1.100, p<0.0001) Elevated ALP level (HR=1.553, 95%CI 1.142-2.112, p=0.005) Baseline sum of longest diameters of target lesions (HR=1.004, 95%CI 1.001-1.006, p=0.007) Elevated TSH level (HR= 0.555, 95%CI 0.422-0.730, p<0.0001) Hypercholesteremia (HR=0.720, 95%CI 0.534-0.971, p=0.031) Hypertension (HR=0.482, 95%CI 0.370-0.628, p<0.0001) Hand-foot skin reaction (HR=0.489, 95%CI 0.373- 0.643, p<0.0001) Elevated LDL level (HR=0.630, 95%CI 0.437-0.909, p=0.014) Age (HR=0.987, 95%CI 0.975-0.999, p=0.039) OS Ratio of granulocytes to lymphocytes at PD (HR=1.116, 95%CI 1.081-1.151, p<0.0001) Baseline sum of longest diameters of target lesions (HR=1.006, 95%CI 1.003-1.008, p<0.0001) ECOG PS≥2 at PD (HR=2.245, 95%CI 1.704- 3.508, p<0.0001) Elevated TSH level (HR=0.725, 95%CI 0.524- 1.005, p=0.053) Hypertriglyceridemia (HR=0.601, 95%CI 0.440-0.821, p<0.0001) Rash (HR=0.581, 95%CI 0.369-0.916, p=0.019) Female (HR=0.713, 95%CI 0.533-0.953, p=0.022)
Conclusion:
This analysis explored the possible impact factors of PFS and OS in Anlotinib treatment. Moreover, we provide real data for the prediction of Anlotinib efficacy and most benefit population through the baseline characteristics and variety of clinical index. However, further analysis in the larger scale study is still looking forward.
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-006 - Efficiency of Anlotinib as 3rd Line Treatment in Patients with Different EGFR Gene Status, an Exploratory Subgroup Analysis of ALTER0303 Trial (ID 8306)
09:30 - 09:30 | Author(s): Ying Cheng
- Abstract
Background:
Anlotinib hydrochloride is a novel TKI targeting the VEGFR, FGFR, PDGFR and c-Kit. ALTER0303 trial (NCT02388919), phase III study has demonstrated that Anlotinib significantly prolonged OS and PFS in advanced NSCLC patients as 3[rd] line treatment. Here we report the efficacy of anlotinib in patients with or without EGFR gene mutations from the ALTER0303 trial.
Method:
Eligible adult IIIB/IV NSCLC patients who progressed after at least 2 lines of prior therapies were randomized 2:1 to receive Anlotinib or placebo (12 mg QD from day 1 to 14 of a 21-day cycle) till progression. Patients harboring EGFR or ALK mutations must had received previous targeted therapies. Primary endpoint is OS.
Result:
Among patients with sensitive EGFR mutations, the PFS was 0.83 months for control arm and 5.57 months for anlotinib arm (p<0.0001, HR=0.15, 95%CI: 0.09-0.24). Accordingly, OS was found 4.43 months longer in anlotinib group (6.27 vs 10.70, p=0.0227, HR=0.59, 95%CI: 0.37-0.93). On the other hand, in the subgroup of patients with wild-type EGFR gene, remarkable advantages in PFS and OS were observed as well. Specifically, PFS in control arm was 1.57 months which is 3.80 months shorter than that in anlotinib group (1.57 vs 5.37, p<0.0001, HR=0.29, 95%CI: 0.22-0.39). As to OS, superiority of 2.40 months was found in anlotinib arm (6.47 vs 8.87, p=0.0282, HR=0.73, 95%CI: 0.55-0.97). In the patients treated with Anlotinib, the most common (≥ 3 grade) and significantly differ from placebo group AEs were hypertension (13.61%), dermal toxicity (3.74%) and hypertriglyceridemia (3.06%). These results indicate that either the patient with EGFR mutation or not, they can both benefit from Anlotinib treatment.
Conclusion:
In ALTER0303 trial, significant advances in OS and PFS were found in anlotinib treated patients from both subgroups (sensitive EGFR mutations and wild EGFR gene type), indicating that, independent of the EGFR gene status, anlotinb treatment led to a consistent improvement in OS and PFS for advanced NSCLC patients and may be an appropriate option for this difficult-to-treat population as 3[rd] line treatment.
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P3.03-017 - Blood Samples NGS for Baseline Molecular Signature of Anotinib Treated Advanced NSCLC Patients in ALTER0303 Trial (ID 9670)
09:30 - 09:30 | Author(s): Ying Cheng
- Abstract
Background:
Anlotinib hydrochloride, an oral multi-target TKI targeting VEGFR, FGFR, PDGFR and c-Kit, have demonstrated noticeable effects for advanced NSCLC as 3[rd] line treatment in phase III trial (ALTER0303). Anlotinib significantly improved OS (9.63 vs. 6.30 months, p=0.0018, HR=0.68) and PFS (5.37 vs 1.40 months, p<0.0001, HR=0.26) comparing to placebo. Here, we applied ctDNA-based NGS to investigate the association between baseline molecular signature and clinical parameters.
Method:
Blood samples were collected from patients who enrolled in Anlotinib arm in ALTER0303 trial. Total of 92 samples were analyzed by capture-based targeted ultra-deep sequencing using a panel consisting of critical exons and introns of 168 NSCLC-related genes for the baseline genetic profiling.
Result:
At baseline, ctDNA was detected in 85% samples (78/92), driver mutation was found in 58% (53/92) samples. POM121L12 and CDKN2A mutations showed a tendency of co-occurrence with TP53, and mutually exclusivity was found between KEAP1 and TP53. The correlation between baseline molecular signature and treatment efficacy measured by PFS or best response was also investigated. Maximum mutation allele frequency (MAF) at baseline was inversely correlated with PFS (P=0.006, HR=0.612, 95%CI: 0.402-0.932). Patients achieving SD or PR had a significantly lower MAF comparing to patients having PD as their best response (p=0.018). Tumor mutation burden (TMB) is positively correlated with age (p=0.016) and gender (p=0.01). POM121L12, TP53 and MYC statuses are correlated with metastases burden. Moreover, as an important drive gene, EGFR mutation and/or EGFR amplification was found in 36 patients at baseline. In 27 patients with sensitizing EGFR mutation (L858R or 19 del), no significant differences was found in PFS compare to those without this mutation (n=65) (5.53 vs 5.53 months, p=0.495, HR=1.16, 95%CI: 0.73-1.85). As well, no significant difference was found in PFS between the patients with (n=17) or without EGFR T790M mutation (5.53 vs 5.53 months, p=0.253, HR=1.35, 95%CI: 0.75-2.41). Interestingly, in patients with EGFR amplification (n=10), the PFS is significantly shorter than those with normal EGFR copy number (2.12 vs 5.57 months, p=0.002, HR=2.70, 95%CI: 0.99-7.36). However, a tendency of PFS benefit is still observed in patients with EGFR amplification treated by Anlotinib comparing placebo arm in ALTER0303 (1.40 months).
Conclusion:
According to available data, no correlation was found between PFS and EGFR sensitizing mutations or T790M in anlotinib treatment. The negative correlation of EGFR amplification and PFS is still need verification to eliminate the bias caused by the disparity and limitation of samples. A larger scale analysis is ongoing.
