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Ye Guo



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    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 3
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-103 - Long-Term Response to Second-Line Afatinib for the Treatment of Advanced Lung Squamous Cell Carcinoma (Now Available) (ID 2962)

      08:00 - 18:00  |  Presenting Author(s): Ye Guo

      • Abstract
      • Slides

      Background

      Lung squamous cell carcinoma (SqCC) with large heterogeneity and complex genetic map accounts for 25–30% of non-small-cell lung cancer (NSCLC) cases. SqCC is lack of defined molecular targets and often diagnosed at a advanced stage, which contribute to poor prognosis. Afatinib is an irreversible ErbB family inhibitor that is approved for the second-line treatment of patients with advanced SqCC who progressed after platinum-based chemotherapy based on the significant clinical benefits in Lux-Lung8.

      Method

      We presented a case of a 56-year-old male with a 30-year history of smoking was diagnosed as SqCC of the left lung (cT2N3M0, IIIB). After neoadjuvant chemotherapy +sugery + adjuvant chemotherapy, CT scans showed disease progressed with disease-free survival (DFS) of 12 months. Thus, continuous chemoradiotherapy was administered. Seven months later, chest CT suggested that the disease progresssed again. Subsequently, the patient was enrolled into LUX-Lung 8 study and began the second-line therapy of afatinib (40 mg/day).

      Result

      The patient remaining in stable disease (SD) after 8 weeks and achieving complete response(CR) after 12 weeks treatment.The patient is still alive and the disease has not progressed more than 5 years since initiation of treatment. There‘s no obvious side effects during the treatment.

      Conclusion

      We found that the patient had a favorable progosis with the overall survial of more than five years treated with afatinib. Long-term response to afatinib in this case provides an important reference for the treatment of patients with advanced SqCC.

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      EP1.01-106 - A Special Case of Synchronous Multiple Primary Lung Cancer with Mediastinal Lymph Node Metastases of Unknown Primary Origin (Now Available) (ID 2101)

      08:00 - 18:00  |  Author(s): Ye Guo

      • Abstract
      • Slides

      Background

      Coexisting lung cancers that are independent of each other and have either different or the same histology type are designated synchronous multiple primary lung cancer (sMPLC). The incidence of sMPLC is 0.2%-8% and has been increasing due to the recent development of early detection technology. Cancer of unknown primary site (CUP) accounts for 3%-5% of cancers, it rarely occurs in mediastinal lymph nodes and accounts for only 1.0−1.5% of all CUP cases.

      Method

      We presented a 61-year-old man with a history of smoking and old tuberculosis. The image data showed a large mass (2.4 cm*2.3 cm*2.0 cm) in the left lower lobe, and the 5th group of mediastinum lymph nodes was enlarged, suggesting peripheral lung cancer with lymph node metastasis. Multiple GGNs had been found in both lungs and the tuberculosis in the upper lobes of both lungs was identified. No other distant metastases were detected from other image data. Left lower lobe resection and lymph node dissection were performed on the patient.

      Result

      Intraoperative pathology revealed squamous cell carcinoma with no driver mutations in the left lower lobe. Adenocarcinoma harbouring the EGFR gene exon 18 mutation (G719A/G719C) was diagnosed in the mediastinum lymph node dissection. Multiple gene sequencing showed that there’s no relationship was between two primary sites. The hypothesis of the primary origin of the metastatic mediastinal lymph nodes is scar cancer from tuberculosis or multiple GGNs. Chemotherapy consisting of four cycles of gemcitabine plus cisplatin were prescribed for this patient after the operation. The current status of the patient was evaluated as stable disease (SD) with a PFS of more than 12 months.

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      Conclusion

      We found a sMPLC patient with different pathological types between the lung and lymph node lesions. Lung scar cancer or GGNs is highly suspected to be the origin of the metastatic mediastinal lymph node.

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      EP1.01-59 - The Effectiveness of Osimertinib in a NSCLC Patient with Complex Uncommon EGFR Mutations of G719X and S768I: A Case Report (Now Available) (ID 2535)

      08:00 - 18:00  |  Author(s): Ye Guo

      • Abstract
      • Slides

      Background

      With the deeper and wider application of gene detection technology in lung cancer, an increasing number of genetic alterations have been identified, especially in the epidermal growth factor receptor (EGFR) gene, including uncommon and complex types of EGFR gene mutations; however, the efficacy of the targeted therapy in these gene mutation types is not clear.

      Method

      We report the genetic test results from the analysis of postoperative specimens from a lung adenocarcinoma patient that suggest complex EGFR mutations of G719X and S768I.

      Result

      After tumor recurrence, the patient was treated with osimertinib and achieved an excellent and long-lasting clinical response. The patient has taken osimertinib for 18.2 months with an efficacy evaluation partial response (PR), and her follow-up is still ongoing.

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      Conclusion

      Complex uncommon EGFR mutations of G719X and S768I have a good response to osimertinib.

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    EP1.04 - Immuno-oncology (ID 194)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.04-36 - Aggravation of Depigmentation for a NSCLC Patient with Pre-Existing Vitiligo Using Immune Check Point (PD-1) Inhibitor: A Case Report (Now Available) (ID 2517)

      08:00 - 18:00  |  Author(s): Ye Guo

      • Abstract
      • Slides

      Background

      Immune checkpoint inhibitors (ICIs) such as anti-PD-1/PD-L1/CTLA4 antibody can enhance the antitumor activity of the immune system by mainly promoting CD8+ T lymphocyte immune function. While, they can also induce immune-related adverse events (irAEs), especially the skin toxicity, such as maculopapular rash, lichenoid reactions, vitiligo and pruritus. However, the effectiveness and safety of ICIs in cancer patients who are also suffered from autoimmune diseases are still unclear.

      Method

      In our present report, we described a newly diagnostic non-small cell lung cancer (NSCLC) patient who suffered from the focal vitiligo for about ten years, her vitiligo lesions were localized in eyes and mouth circumference.

      Result

      The patient’s vitiligo was aggravated rapidly with depigmentation of the whole body skin in just half a year. Meanwhile, lung cancer focus was still in a stable status for over 14 months. The efficacy evaluation is stable disease (SD), but as the treatment time prolonged, the tumor density gradually decreased, suggesting that the immunotherapy continues to benefit.

      Conclusion

      Vitiligo, as one kind of autoimmune diseases, should be paid more attention as using with ICIs at the same time. Meanwhile, ICIs may bring more irAEs and more benefit in the pre-existing autoimmune disease population, compared with that normal population.

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    EP1.14 - Targeted Therapy (ID 204)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.14-48 - Efficacy and Safety of Afatinib Plus Apatinib Combination Therapy for a Lung Adenocarcinoma Patient with Her-2 V659D Mutation (Now Available) (ID 1706)

      08:00 - 18:00  |  Author(s): Ye Guo

      • Abstract
      • Slides

      Background

      In lung cancer,several literature report the rare transmembrane domain mutations occur in V659D of Her-2 may be effective for afatinib. This is a successful case of a lung adenocarcinoma patient with a novel Her-2 V659D mutation but unsatisfactory efficacy with afatinib treated with afatinib plus apatinib.

      Method

      A 73-year-old Chinese man with a heavy-smoking history came to our hospital due to"Intermittent cough"in eary March 2017. He was diagnosed with stage IB(T2aN0M0)lung adenocarcinoma by pathology of left upper lobectomy in 29th Mar 2017(Fig.1). An HER-2 mutation(V659D mutation)was detected in the surgical specimen by Next-generation sequencing (mutation abundance is 44.6%).

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      Recurrence of lung cancer occurred after 16 months on 30th July 2018. Pulmonary CT revealed multiple nodules in both lungs( Fig.2). The patient had no intention of chemotherapy. Daily oral doses of 40 mg of afatinib were given on 31st July 2018. Twenty-two days later, a CT scan revealed the bilateral pulmonary nodules were slightly smaller, however cough symptoms were worse than before(Fig.3). On 23rd Agu 2018, considering the efficacy and side effects, he started taking afatinib(reduced to 30mg)combined with apatinib(500mg/day). The chest CT scan revealed the metastases continued to shrink after 1 month, and necrotic cavities appeared in the middle of the lesions(Fig.4). Cough symptoms improved obviously. Therapeutic evaluation was stable. He had no progression of the disease for months.

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      Result

      On 21st Feb 2019, lung CT indicated enlargement of bilateral pulmonary nodules and new lesions suggesting disease progresses. Progression-free survival is 6.1 months. As for the side effects, he had two-grade rash on the face, three-grade oral mucositis with afatinib monotherapy. And he had one-grade rash on the face, two-grade oral mucositis and two-grade hand-foot syndrome in the combined treatment of afatinib and apatinib.

      Conclusion

      Afatinib combined with apatinib is a safe therapeutic method for rare mutation of HER-2 V659D that can increase the efficacy.

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      EP1.14-50 - The Effectiveness of the Combined Therapy of Osimertinib and Vemurafenib in a Patient with Coexistance of EGFR and BRAF Mutation (Now Available) (ID 2501)

      08:00 - 18:00  |  Author(s): Ye Guo

      • Abstract
      • Slides

      Background

      With the widely application of gene detection techonology in lung cancer, more rare genetic alterations are indentified, including the coexistance of double driver mutations. The coexistance of EGFR and BRAF mutations in lung cancer is rare and its treatment strategy has not been systemetically explored. Synergistic inhibition of the tumour cells by EGFR-TKI combied with BRAF inhibitor has been proved in a vitro trail. If there's clinical benefit of the combined tharepy targeting EGFR and BRAF pathways is unclear.

      Method

      We present an adenocarcinoma lung cancer patient harboring 19 exon deletion and T790M mutation of EGFR who progressed on osimertinib with an emergence of BRAF VE600 mutation. The treatment of single-agent vemurafenib is effective for the metastatic leision but make the primary leision progession. Given the progression of primary leision the was noted, osimertinib was added to vemurafenib for treatment.

      Result

      During the first week of combined therapy of osimertinib and vermurafenib with oral dose of 80 mg qd and 960mg bid respetively, the patient developed intolerable palpitation and fatigue (grade 3), which were related to drugs. Therefore, the dose of vemurafenib was reduced to 960mg qd, and osimertinib was taken with the original dose (80mg qd). Subsequently, aboved adverse events were obviously relieved (grade 1). After three months of combined therapy, the size of the priamry leision reduced significantly and the patient achieved a partial reponse, suggesting the the effectiveness of the combined therapy of osimertinib and vemurafenib. Currently, the follow-up of the patient is ongoing

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      Conclusion

      This case provides an example of the successful treatment of the combination of vemurafenib and osimertinib, and highlights the potential value of BRAF inhibitor combined EGFR-TKIs in the treatment of advanced lung cancer harboring BRAF mutation and EGFR mutation.

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    P1.12 - Small Cell Lung Cancer/NET (ID 179)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.12-14 - Phase II Trial of Apatinib Plus Chemotherapy for Second-Line and Above Treatment of Advanced SCLC: Focus on Efficacy and Safety (Now Available) (ID 1788)

      09:45 - 18:00  |  Author(s): Ye Guo

      • Abstract
      • Slides

      Background

      Small-cell lung cancer (SCLC), which accounts for 15% of all lung cancers, is characterised by its rapid proliferation. The clinical outcomes of second-line and above treatments are unsatisfactory, resulting in a median progression-free survival (PFS) of less than 3 months. There is currently none targeted drugs or new chemotherapeutic drugs that can achieve breakthroughs in advanced SCLC. This study aims to observe whether apatinib in combination with chemotherapy can be a new choice for second-line and above treatment of advanced SCLC.

      Method

      This is a prospective, single-center, single-arm clinical study designed to evaluate the efficacy and safety of apatinib plus chemotherapy for second-line and above treatment of advanced SCLC (ClinicalTrials.gov NCT03547804). Patients received 500mg apatinib qd orally, if the patient has a grade 3/4 adverse reaction during the treatment, it can be reduced to apatinib 250mg qd orally. Chemotherapeutic agents are limited to irinotecan or docetaxel alone. The primary endpoint was the progression-free survival (PFS). The secondary endpoints included overall survival (OS), disease control rate (DCR), objective response rate (ORR), and adverse events (AEs).

      Result

      Twenty patients were enrolled from March 2018 to March 2019. Fifteen patients were available for response evaluation. The ORR and DCR were 33.33% (5/15) and 93.33% (14/15), respectively. The predicted median PFS time was 5.8 months (95% confidence interval [CI] 5.1-6.5 months) (SPSS 20.0 software). The most common treatment-related AEs were neutropenia (45.0%), leucopenia(35.0%), abnormal liver function (20%), nausea and vomiting (20%) and thrombocytopenia (20.0%), without any treatment-related deaths. It is worth noting, 12 patients underwent apatinib reduction due to grade 3/4 adverse reactions.

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      Conclusion

      Apatinib plus single agent chemotherapy showed promising efficacy in a patients with advanced SCLC who had failed chemotherapy. And the recommended phase II dose of apatinib as combination therapy was 250 mg qd.

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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-46 - PI3K/AKT Signal Pathway Regulates Malignant Transformation of MPLC with EGFR-Sensitive Mutation (Now Available) (ID 2456)

      10:15 - 18:15  |  Author(s): Ye Guo

      • Abstract
      • Slides

      Background

      Multiple primary lung cancer (MPLC) is a presumed uncommon entity, but its true incidence, ranging from 0.2% to 8%, is increasing as the result of the widespread use of early detection tools. MPLC displays diverse clinical trajectories and genomic profiles. The in-depth study on the mechanism of malignant transformation of MPLC will provide new ideas for the future treatment of MPLC.

      Method

      In this study, we analyse the genomic profiles of 25 tumors and 12 adjacent tissues from 10 patients with MPLC who underwent surgical resection through the whole-exome sequencing (WES).

      Result

      Ten patients were enrolled in this study, one patient with different evolutional stages of the same disease (AAH, MIA, and IA) and one patient with completely different pathologies (adenocarcinoma and squamous cancer). Eight patients with different driver genes (EGFR exon 19 deletionexon 21 L858R mutation and exon 21 L861Q mutation) of lung adenocarcinoma. We observed different mutational landscapes between tumors in the same patient by analyzing somatic mutations, copy number variations, clonal structures, and signal transduction pathways. Most tumors showed significant APOBEC mutant patterns, especially C→T transversions (Figure 1). Moreover, we also found that EGFR exon 19 and 21 mutations enrich different signal pathways. The PI3K/AKT signal pathway is often be enriched in tumors with EGFR exon 19 deletion, which is closely related to the early progression of the tumor. While PTEN kinase activation is associated with EGFR exon 21 L858R mutation (Figure 2). MPLCs with EGFR wild-type may be associated with abnormal regulation of signal pathways, including SOS1, JAK-STAT and others.

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      Conclusion

      This study suggests that the different "gene mutation trajectories" of EGFR exon 19 and 21 mutations are closely related to the genetic heterogeneity of MPLC. Besides thatAPOBEC mediated mutations may play an important role in the initial malignant transformation of tumors.

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