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Yi Zhao
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MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 107
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MA15.05 - The Mutational Profiles of EGFR 19 Exon Deletion and 21 Exon L858R Mutation and Their Association with Primary Response to EGFR-TKIs (ID 12671)
14:00 - 14:05 | Author(s): Yi Zhao
- Abstract
- Presentation
Background
In addition to the known resistant genetic alterations, such as de novo T790M and TP53 mutations, some recent studies suggested that other concomitant mutations might also compromise the efficacy of EGFR-TKIs. Meanwhile, it has been widely observed that EGFR 19 exon deletion (19del) was associated with better outcomes in treatments with EGFR-TKIs than L858R mutation (L858R). It is of interest to explore whether the respective mutational profiles of 19del and L858R may explain their different sensitivity to EGFR-TKIs.
a9ded1e5ce5d75814730bb4caaf49419 Method
We obtained individual patient data from 7 studies (including 1 from our center) using next generation sequencing to comprehensively determine the mutational profile of EGFR mutated patients. As different panels were used by different studies, we analyzed T790M, TP53 and the loci that were reported by at least 4 studies (half of the included ones).
4c3880bb027f159e801041b1021e88e8 Result
A total of 250 19del and 279 L858R patients were included. We found similar prevalence of all co-mutations (19del 65.2% vs. L858R 64.2%), TP53 (19del 36.8% vs. L858R 40.9%), APC, BRAF, PIK3CA, STK11, PDGFRA, PTEN, AKT1 and KIT between the two types, except for de novo T790M (19del 34.4% vs. L858R 50%, P=0.07), CDKN2A (19del 10.5% vs. L858R 3.4%, P=0.03) and KRAS (19del 0.5% vs. L858R 4.0%, P=0.01). In addition, the number of co-mutations was equivalent between the two types (19del 0.95±0.95 vs. L858R 0.93±0.90, P=1.00). Through multivariate logistic regression, we found that EGFR mutation type, de novo T790M, TP53 and other co-mutations, all had independent adverse effects on primary response rate. Consistently, we found that in those without co-mutations, 19del still showed better outcomes compared with L858R (pure EGFR mutations: 19del 88.0% vs. L858R 68.4%), and that the response rates in both mutation types decreased in the same extent when contaminated with other mutations (EGFR mutations with co-mutations: 19del 53.1% vs. L858R 30.0%).
8eea62084ca7e541d918e823422bd82e Conclusion
Our study demonstrated that the presence of T790M, TP53 and other concomitant mutations indicated poor response to EGFR-TKIs, but most of them showed similar prevalence between 19del and L858R. Patients with L858R showed significantly less response than those with 19del regardless of the co-mutation status, indicating that some intrinsic factors and potentially de novo T790M, rather than other co-mutations, might underlie the different sensitivity of 19del and L858R to EGFR-TKIs.
6f8b794f3246b0c1e1780bb4d4d5dc53Only 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.
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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
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P1.15-17 - Risk Factors of Local Recurrence in EGFR-Mutant Stage III-pN2 Adenocarcinoma After Complete Resection: A Multi-Center Real-World Cohort Study (ID 12740)
16:45 - 18:00 | Author(s): Yi Zhao
- Abstract
Background
Postoperative radiotherapy (PORT) of complete resected stage IIIA non-small cell lung cancer with N2 nodal involvement remained contentious. Our previous study suggested low locoregional recurrences in epidermal growth factor receptor (EGFR) mutant patients. We sought to launch a multi-center large cohort study to evaluate the risk factors of locoregional recurrence in R0 resected EGFR mutant III-pN2 patients without PORT, producing evidence for the design of adjuvant regimens.
a9ded1e5ce5d75814730bb4caaf49419 Method
Three-hundred and fifty-nine consecutive patients with complete resected, pathological approved stage III-pN2 lung adenocarcinoma with sensitive EGFR mutation (exon 19 or exon 21) have been investigated. Patients were excluded if they received induction therapy (7.5%) or PORT (9.6%). Three hundred cases have been analyzed. Clinicopathologic characteristics, pretreatment work-ups, EGFR mutant status and patterns of failure were documented. Patients were sub-staged by the International Association for the Study of Lung Cancer (IASLC)/ the Union for International Cancer Control (UICC) 7th classification on N2 disease. Risk factors of locoregional recurrence-free survival (LRFS) were evaluated by univariate and multivariate analyses.
4c3880bb027f159e801041b1021e88e8 Result
According to IASLC/UICC 7th classification, there were 198 (66.0%) patients with unforeseen N2 (N2a), 36 (12.0%) with minimal/single station N2 (N2b), 41 (13.7%) with selectively centrally located N2 (N2c) and 25 (8.3%) with bulky and/or multilevel N2 (N2d). After surgery, 70 (23.3%) patients were treated with adjuvant tyrosine-kinase inhibitors (TKIs), while other 230 (76.7%) were free from adjuvant TKIs. With median follow-up of 28.5 (range：6-133) months, the 2-year LRFS, distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 88.3%, 65.3%, 57.7% and 89.7%. Ultimately, 15.7% (47/300) patients developed locoregional recurrences. Distant metastasis was the predominant failure pattern. Multivariate analysis indicated that N2d disease (HR: 2.65, p=0.030) and extranodal extension (HR: 3.48, p<0.001) were risk factors of LRFS.
8eea62084ca7e541d918e823422bd82e Conclusion
R0 resected stage III-pN2 NSCLC patients with sensitive EGFR mutation (exon 19 or exon 21) tended to present limited N2 disease and low locoregional recurrences. Patients without bulky N2, multilevel N2, and extranodal extension might be refrained from PORT. Further studies evaluating the optimal radiotherapy approach for completely resected N2-positive NSCLC are required for validation.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-01 - The Impact of Anlotinib on Brain Metastases of NSCLC: Post-Hoc Analysis of a Phase III Randomized Control Trial (ALTER0303) (ID 12454)
16:45 - 18:00 | Author(s): Yi Zhao
- Abstract
Background
Few evidence has measured the intracranial impact of multitargeted VEGFR-TKIs. Anlotinib hydrochloride, which targets VEGFR, PDGFR, FGFR and c-Kit, has been shown to significantly prolong PFS and OS compared with placebo as second/third-line treatment for NSCLC in a randomized, double-blind, phase Ⅲ trial (NCT02388919). Herein we sought to analyze anlotinib’s effect in managing brain metastases (BM) and its brain-associated toxicities.
a9ded1e5ce5d75814730bb4caaf49419 Method
The PFS/OS of anlotinib versus placebo in those with and without BM records at baseline were calculated and compared respectively. In addition, time to brain progression (TTBP), a direct indicator of intracranial control, was also compared between anlotinib and placebo. All calculations were adjusted for confounding factors, including stage, histology, driver mutation type, etc.
4c3880bb027f159e801041b1021e88e8 Result
A total of 437 patients (294 receiving anlotinib; 143 receiving placebo) were included. 97 cases (22.2%) were recorded to have BM at baseline. There were more BM cases among younger patients and those with adenocarcinoma. Both of the benefit magnitude from anlotinib over placebo were similar between BM and non-BM group in terms of PFS (BM: HR 0.19, 0.11-0.34; non-BM: HR 0.29, 0.22-0.37; interaction P=0.691) and OS (BM: HR 0.71, 0.44-1.16; non-BM: HR 0.67, 0.51-0.89: interaction P=0.789). More specifically, anlotinib was associated with significantly longer TTBP (HR 0.11, 95% CI 0.03-0.41, P=0.001; Figure1) despite all confounders, indicating a 90% reduction of brain progression risk from anlotinib. Interestingly, anlotinib was also associated with more neural toxicities (18.4% vs. 8.4%, P=0.007) and psychological symptoms (49.3% vs. 35.7%, P=0.008) compared with placebo, especially headache (P=0.01), brain edema (P=0.04) but not infarction or cerebral hemorrhage. The above results were all confirmed both in intention-to-treat and per-protocol population.
8eea62084ca7e541d918e823422bd82e Conclusion
Anlotinib can benefit NSCLC patients with brain metastases and is highly potent in managing intracranial lesions. Its special effect on brain metastases and cerebral tissues merits further investigation.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-16 - Preference of Adjuvant Treatments for EGFR-Mutant Resected NSCLC Patients: Results of a National-Wide Survey in China (ID 13390)
16:45 - 18:00 | Author(s): Yi Zhao
- Abstract
Background
EGFR mutated patients represent half of NSCLC cases in China. ADJUVANT study (NCT01405079), a published multicenter RCT, showed that EGFR-TKIs were associated with significant longer DFS than chemotherapy in stage II to IIIA resected NSCLC patients. We sought to investigate the preference on adjuvant EGFR-TKI of the surgeons specializing on NSCLC in China by conducting an online national-wide survey.
a9ded1e5ce5d75814730bb4caaf49419 Method
The question ‘would you recommend EGFR-TKIs as adjuvant therapy in postoperative patients with EGFR mutation? -Yes; No’ was included on an online survey system. Interviewee personal information was also collected. Logistic regression model was conducted to explore factors associated with the choices.
4c3880bb027f159e801041b1021e88e8 Result
We received 732 responses from lung cancer surgeons from 30 provinces of China, 618 (84.43%) doctors were from department of general thoracic surgery and 114 (15.57%) surgeons from department of thoracic oncology surgery, 660 (90.16%) were from tertiary hospitals and 65 (8.88%) from the secondary ones. The interviewees consisted of 93 (12.70%) master candidates, 15 (2.05%) doctoral candidates, 98 (13.39%) residents, 217 (29.64%) attending doctors, 174 (23.77%) associate chiefs of surgeon and 135 (18.44%) chiefs of surgeon. As a result, 572 (78.1%) surgeons selected “Yes”, 143 (19.5%) selected “No”, and the rest abstained. Logistic regression analysis revealed that the result was not influenced by different career duration, location, economic status of living, hospital grade, department type, etc.
8eea62084ca7e541d918e823422bd82e Conclusion
This national-wide large sample survey showed that recommending EGFR-TKIs as adjuvant therapy for postoperative EGFR-mutant NSCLC patients was widely supported by specialists in lung cancer in China.
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