Browsing Over 990 Presentations
493P - Is exon 19 deletion different from exon 21 mutation in advanced non-small cell lung cancer: A single centre experience
- Sarita Shrivastva
- Sarita Shrivastva
- Bala Stalin
- Sadashivudu Gundeti
Abstract
Background
Epidermal growth factor receptor (EGFR) deletion of exon 19 and exon 21 mutations are the most common mutations in advanced non-small cell lung cancer (NSCLC) and predict higher sensitivity to EGFR tyrosine kinase inhibitors (TKI). The present study is a retrospective analysis of patients harboring EGFR exon 19 deletions and exon 21 mutations in advanced NSCLC.
Methods
Data of patients diagnosed with advanced NSCLC patients with EGFR mutations from January 2012 to March 2019 was analysed. EGFR mutation analysis was performed using DNA sequencing by real time polymerase chain reaction method. Exon 19 and exon 21 mutated patients were compared for clinicopathological features and outcomes.
Results
Data of 697 patients with lung cancer was retrieved of which 613 patients had advanced NSCLC. A total of 441 patients were evaluated for EGFR mutations and 135 (30.6%) patients were positive for EGFR mutations. The median age at presentation was 57.5 years(range, 30-88). Smoking history was seen in 38 (28.1%) patients and 97 (71.8%) were non smokers. Of these 135 patients with EGFR positivity, 129(95.6%) had adenocarcinoma histology and 6(4.4%) had adenosquamous histology. Exon 19 and exon 21 mutations accounted for 79(58.5%) and 45(33.33%) cases respectively. Mutations in exon 18, exon 20 and double mutations were seen in 2(1.4%), 3(2.2%) and 6(4.4%) patients respectively. Thirty nine (28.8%) patients received initial chemotherapy followed by switch maintenance. Geftinib (82.2%) was the most common TKI used followed by erlotinib (9.6%), Afatinib (4.5%), Osimeritinib (0.8%) and chemotherapy (2.9%). The clinical profile, treatment details and outcomes are tabulated below. The median PFS and OS were 8.9 months (range, 4-42 months) and 18 months (range,4-46 months) respectively. Table: 493POverall EGFR Positive(n = 135) Exon 19 deletions(n = 79) Exon 21 Mutated (n = 45) P Value Median Age (years) 57.5 (range, 30-88) 55 (range, 35-88) 61 (range, 30-80) Sex: Male Female Ratio 75 60 1.25:1 44 35 1.25:1 25 20 1.25:1 0.98 Smoker: Yes No 38 97 26 53 11 34 0.32 Metastases: Bone B/L lung Pleural effusion Brain Liver 67 58 40 22 10 39 32 22 20 8 26 22 13 2 1 0.36 0.38 0.9 0.03 0.24 Rash Grade 1 Grade 2 Grade 3 37 20 10 7 23 8 10 5 13 11 0 2 0.8 Response evaluated Partial response Stable disease Progressive disease 111 48 (43.3%) 49 (44.1%) 14 (12.6%) 65 27 (41.6%) 31 (47.7%) 7 (10.7%) 38 18 (47.4%) 16 (42.1%) 4 (10.5%) 0.5 0.6 0.7 Median PFS (months) 8.9 9.2 8.3 0.8 Median OS (months) 18 18.9 17 0.5
Conclusions
In patients with EGFR-sensitizing mutations, tyrosine kinase inhibitors offer superior progression free survival and response rates and are well tolerated. Brain metastases at presentation were significantly higher in exon 19 compared to exon 21. No significant differences were observed in median PFS or median OS in EGFR exon 19 deleted or Exon 21 mutated subgroup.
Legal entity responsible for the study
Department of Medical Oncology, Nizam\'s Institute of Medical Sciences.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
47P - Investigation of the use of a novel S-1 administration method for treating metastatic and recurrent breast cancer
- MAYUKO MIKI
- MAYUKO MIKI
- Shintaro Takao
- Muneharu Konishi
- Yasushi Shigeoka
- Masaru Miyashita
- Hirohumi Suwa
- Michiko Imamura
- Toshitaka Okuno
- Koichi Hirokaga
- Yasuo Miyoshi
- Keiko Murase
- Ayako Yanai
- Kazuhiko Yamagami
- Kohei Akazawa
Abstract
Background
When considering treatment for metastatic and recurrent breast cancer, it is necessary to select drugs with emphasis on side effects and QOL. In Japan, oral 5-FU drugs have often been used for initial treatment. In the conventional schedule of S-1 for 4-week administration period followed by 2-week rest, the inferiority of S-1 to T has already been proved. In this study, we examined the efficacy and safety of the schedule of S-1 for 2-week administration period followed by 1-week rest, which is considered to have less side effects and better compliance.
Methods
We enrolled individuals with HER2-negative breast cancer who had not received chemotherapy after diagnosis of metastatic breast cancer. S-1 (40-60 mg, twice daily) was administered consecutively for 14 days followed by 7 days of rest (1 course). The primary endpoint was progression-free survival (PFS); the secondary endpoints were overall survival (OS), time to treatment failure (TTF), response rate (RR), disease control rate (DCR), and adverse events.
Results
Between September 1, 2013 and August 31, 2016, 32 patients were enrolled. Median PFS was 7.8 months (1.4-35.4 months), and median OS was 25.2 months (4.8-47.8 months). TTF was 9.1 months. RR was 31.3%, and the DCR was 78%. The cumulative rates of the relative total administration dose of S-1 was 95.6%. Incidence of grade 3 side effects were neutropenia (9.4%), leukopenia (3.1%), anorexia (3.1%), ocular symptoms (3.1%), and an increase in total bilirubin levels (3.1%).
Conclusions
The schedule of 2-week administration period followed by 1-week rest seems to be safe and effective for primary treatment of metastatic and recurrent breast cancer.
Legal entity responsible for the study
Kobe Breast Cancer Oncology Group.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Changing paradigm of treatment strategy for intermediate and advanced HCC (ID 1834)
301P - Oncological outcome following 3 Drug NACT for Bucco-Alveolar carcinoma with Supra-notch ITF extension
- Karan Gupta
- Karan Gupta
- Dushyant Mandlik
- Kaustubh Patel
Abstract
Background
Bucco-alveolar carcinoma is a clinical entity prevalent in Asia. These cancers have early involvement of Infra-temporal fossa (ITF) and subsequent poor oncological outcomes. Locally advanced Bucco-alveolar complex carcinoma (T4b) with supra-notch (supra-sigmoid) ITF extension is oncological challenge with poor outcome. We analysed oncological outcome in patients managed with 3-drug Neo-adjuvant chemotherapy (NACT) followed with surgical compartmental resection and adjuvant chemoradiation.
Methods
33 cases of T4b Bucco-alveolar complex carcinoma with supra-notch ITF extension included from June 2009 to January 2017. Patients received 3-Drug NACT (3-day regimen: IV Cisplatin 75 mg/m2 or IV Carboplatin 70 mg/m2 + IV Docetaxel 75 mg/m2 + IV 5-FU 1000 mg/m2) for 2-3 cycles every 21 days. Response assessed with clinical examination, improvement in symptoms (improved mouth opening etc.) and Response Evaluation Criteria In Solid Tumors (RECIST) criterion. Patients showing good response on NACT underwent Compartmental surgical resection with complete ITF clearance followed by adjuvant chemoradiotherapy (5-6 cycles weekly Inj. Cisplatin with 60Gy/30# RT). Data analyzed using STATA 13 and Kaplan Meir graphs for survival rates.
Results
31 patients (93.9%) showed response on NACT and underwent Surgery, with 2 patients showing disease progression after 1st cycle of NACT were treated non-surgically with palliative intent. Clinical response according to RECIST criterion & subjective clinical improvement > 50% was noted in 18 cases while < 50% in 13 cases. 22 of 31 patients were disease free with 7 loco-regional recurrences. There were no recurrences in ITF. Overall survival and disease-free survival rate was 81.8% and 70.9% respectively at mean follow-up of 30 months.
Conclusions
3-drug NACT followed by surgical resection in cases showing response to NACT with adjuvant chemoradiation provides a realm of hope for these borderline resectable T4b supra-notch cases. NACT provides an opportunity to attain better microscopically negative resection margins and helps in proper bio-selection of cancers according to their radio-chemosensitivity and response leading to better oncological outcomes.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
PAGA for early breast cancer: Review of adapted recommendations for early breast
- Yeon Hee Park
- Yeon Hee Park
YO29 - Acute kidney injury secondary to bilateral renal artery tumor thrombosis in a case of posterior mediastinal undifferentiated sarcoma: case report
- Ritsu Ibusuki
- Ritsu Ibusuki
- Taishi Harada
- Asushi Shimauchi
- Takafumi Kayukawa
- Daisuke Etoh
- Yuki Okamatsu
- Kazuya Tsubouchi
- Katuhiro Inoue
Abstract
Case summary
A 72-year-old Japanese man presented with symptoms of chest pain and poor appetite. Contrast-enhanced CT scan showed a solid mass (diameter:80mm) with slight enhancement located in the left inferior posterior mediastinum. The mass surrounded the descending aorta at the T8-T10 level, partly infiltrating the aorta. Primary mediastinal undifferentiated sarcoma was diagnosed by CT-guided percutaneous needle biopsy. No distant metastasis was apparent on whole diffusion MRI. He was scheduled to undergo chemo radiotherapy, but 3weeks after the diagnosis, sudden anuria was observed, and his blood test revealed acute kidney injury and hyperkalemia. Contrast-enhanced CT-scan revealed occlusion of bilateral renal artery at its origin, and hemodialysis was immediately performed. We suspected that occlusion was caused by tumor embolism. The patient received catheter-directed thrombolysis to improve his renal function and to confirm diagnosis. Tumor cells identifiable as primary lesion were pathologically recognized from a part of the embolus collected by the catheter, which proves acute kidney injury secondary to bilateral renal artery tumor thrombosis. After the treatment, the renal dysfunction remarkably improved and he was able to be taken off dialysis.
Intravascular tumor thrombus often occurs in the venous system. However, we present a rare case of undifferentiated sarcoma patient with mediastinal origin that developed acute kidney injury due to bilateral renal artery tumor thrombosis and successfully treated with catheter-directed thrombolysis.
80P - The clinical usefulness of a new fat-dissociation method to detect lymph nodes from surgically resected specimen in colorectal cancer: Prospective randomized study
- Shiki Fujino
- Shiki Fujino
- Norikatsu Miyoshi
- Masayuki Ohue
- Masayoshi Yasui
- Masato Sakon
- Nariaki Matsuura
Abstract
Background
Pathological examination is essential to determine the cancer stage in colorectal cancer (CRC) patients, and histological examination of lymph nodes plays a pivotal role in the staging process. We previously reported a new fat-dissociation method (FM) to detect lymph nodes from surgically resected mesentery. It can reduce a fat volume of the mesentery and visualize a structure of vessels and lymph nodes. In this study we examined the effectiveness of the FM compared with a conventional palpation method in CRC.
Methods
A single center, open-label, randomized controlled study was performed at Osaka International Cancer Institute (OICC) in Japan from January, 2014, to December, 2014. Randomization was done via a computer-generated permuted-block sequence, and was stratified by surgical procedures and the dissection area of lymph nodes (ie, D2 or D3). Primary endpoint was set at the time to search lymph nodes. Secondary endpoint was set at the number of lymph nodes and 5-year overall survival (OS).
Results
130 patients were enrolled to this study and randomly assigned in a one to one ratio: 65 to the FM group and 65 to the conventional palpation (CP) group. Searching time were 15.9 (±0.6) minutes in the FM group and 45.1 (±1.5) minutes in the CP group (P < 0.001). In CP group there was correlation between BMI and searching time (P = 0.047). Numbers of lymph nodes were 21.5 (±1.9) in the FM group and 19.6 (±1.4) in the CP group (P = 0.546). In right-side CRC, the number of lymph nodes was more in the FM group (32.6±4.5) than the CP group (21.7±2.6) (P = 0.030). 5-year OS rate was 87% in the CP group and 86% in the FM group (P = 0.952).
Conclusions
A new fat-dissociation method could reduce the time for searching lymph nodes without reducing number of lymph node. It is effective in high BMI patients and right-side CRC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
LBA5 - The role of radiation therapy in clinically node-positive, pathological negative nodes after neoadjuvant chemotherapy in breast cancer patients: In sentinel node biopsy and trastuzumab era
- Ji Hyeon Joo
- Ji Hyeon Joo
- Yongkan Ki
- Su Ssan Kim
Abstract
Background
Although current guidelines recommend deciding on postmastectomy radiation therapy (PMRT) or regional nodal irradiation (RNI) after breast conserving surgery (BCS) depending on initial clinical stages before neoadjuvant chemotherapy (NAC), it is controversial whether adjuvant radiation therapy (RT) can be omitted for patients with excellent response. This retrospective study evaluates if PMRT or RNI after BCS significantly reduces locoregional recurrence rate in patients with clinically positive, pathologic negative lymph nodes (LNs) after NAC.
Methods
From 1999 to 2016, 1831 women with breast cancer underwent NAC and surgery. Of them, 427 patients with clinically node-positive and pN0 disease were analyzed.
Results
Median follow-up was 65.4 months. The 5-year locoregional relapse (LRRFS) and disease-free survival (DFS) rates were 96.9% and 88.3%, respectively. In patients with an initial nodal stage of cN2-3, RT significantly reduced LRR, with a hazard ratio (HR) of 0.132 (p = 0.009). However, RT was not shown to be effective in the cN1 group (HR = 0.893, p = 0.9). RT did not improve DFS, regardless of cN stage. PMRT/RNI was defined as the combined set of patients who received PMRT or received RT, including regional nodal irradiation (RNI) after BCS; the effects of PMRT/RNI were analyzed. PMRT/RNI significantly reduced LRR in the cN2-3 patient group (HR = 0.175, p = 0.03), but there was no significant effect for cN1 disease. Among 173 patients who underwent mastectomy, there were 108 and 65 patients, respectively, who received RT or no RT. Among all patients, PMRT had no effect on LRR (p = 0.7). However, among cN2-3 patients, PMRT significantly lowered LRR (HR = 0.10, p = 0.02), while there was no significant effect in cN1 patients.
Conclusions
In analysis of all patients and of mastectomy patients, RT consistently improved local control rate in the cN2 and higher patient group. Similar results were obtained in the combined analysis of PMRT and RNI after BCS. Therefore, in ypN0 patients graded cN2 or higher, RT including RNI is predicted to be absolutely necessary. No conclusion could be reached for cN1 disease.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
339TiP - PACIFIC-5: Phase III study of durvalumab after either concurrent or sequential chemoradiotherapy (CRT) in patients with stage III NSCLC
- Yi-Long Wu
- Yi-Long Wu
- Lvhua Wang
- Mehmet Ali Nahit Sendur
- Young-Chul Kim
- Zhengfei Zhu
- Ying Cheng
- Peiqi Li
- Yulin Qin
- Euan Macpherson
- Phillip A. Dennis
- Shun Lu
Abstract
Background
Non-small-cell lung cancer (NSCLC) represents >80% of lung cancer cases worldwide and 30% of patients (pts) present with Stage III disease. Historically, platinum-based CRT has been the standard of care (SoC) for such pts, yet outcomes are poor. Durvalumab (durva) is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80. Results from the PACIFIC trial of durva in pts with locally advanced, unresectable, Stage III NSCLC, who did not progress on concurrent CRT (cCRT), showed significant improvements in progression-free survival (PFS) and overall survival (OS) with durva vs placebo (PFS: HR 0.52; 95% CI 0.42–0.65; P < 0.001; OS: HR 0.68; 99.73% CI 0.47–0.997; P = 0.0025), and similar safety profiles (Antonia et al, NEJM 2017; 2018). Consequently, treatment with durva after CRT, the PACIFIC regimen, is quickly becoming the new SoC. However, the PACIFIC trial only assessed pts who had received cCRT, but due to the higher toxicity of this approach, some patients may be better suited to sequential CRT (sCRT). Therefore, the objective of the PACIFIC-5 (NCT03706690) study is to assess durva post-CRT in a broader population, including pts with NSCLC who did not progress following either platinum-based cCRT or sCRT.
Trial design
PACIFIC-5 is a phase 3, randomized, double-blind, placebo-controlled, multicenter study. Approximately 360 pts with histologically or cytologically confirmed Stage III, locally advanced, unresectable NSCLC will be enrolled from China and the rest of the world. Eligible pts have not progressed following definitive, platinum-based cCRT or sCRT, and are in complete response, partial response or have stable disease. Pts are being randomized 2:1 to receive either durva (1500 mg i.v.) every 4 weeks, or placebo, until disease progression, toxicity or withdrawal of consent. The primary endpoint is PFS per blinded independent central review; OS is the key secondary endpoint. Other secondary endpoints include OS24, overall response rate, duration of response, PFS2, PFS12, PFS18, time to distant metastases, pt-reported outcomes, durva pharmacokinetics and immunogenicity, and safety assessments. Recruitment is ongoing.
Clinical trial identification
NCT03706690.
Editorial acknowledgement
Medical writing support during the preparation of this abstract, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Fiona Chaplin, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
Y-L. Wu: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self): Pierre Fabre; Honoraria (self): Pfizer; Honoraria (self): Sanofi; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim. Y-C. Kim: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Boehringer Ingelheim. P. Li: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. Y. Qin: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. E. Macpherson: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P.A. Dennis: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. All other authors have declared no conflicts of interest.
Discussion – European perspective
- Demetris Papamichael
- Demetris Papamichael
Should additional combination or RT-CT be used or is Radiation alone to be recommended? Issues with Concurrent TKIs? SBRT/IO? /Current trials?
- Jose Belderbos
- Jose Belderbos
113P - Dicer contributes to chemoresistance in colorectal cancer via regulating a set of miRNAs and their downstream mRNAs
- Liang-Yi Hung
- Liang-Yi Hung
Abstract
Background
Chemotherapy has a good success rate in colorectal cancer (CRC); however, recurrence of CRC is still frequent due to acquired drug resistance. Dicer, one of the key enzymes of the microRNA (miRNA) biogenesis pathway, may be involved in chemoresistance through regulating the expression of miRNAs. Until now, the role of Dicer in regulating chemoresistance is still unclear.
Methods
Oxaliplatin- or 5’FU-resistant cell lines were established to investigate the molecular mechanism of chemoresistance. Western blot was performed to detect the expression of Dicer; next-generation sequencing (NGS) and cDNA array were performed to identify the alternative expression of miRNAs and mRNAs; and RT-qPCR or TaqMan PCR was used to validate the expression of potential miRNAs or mRNAs. Functional characterization of drug-resistant cells was performed by cell proliferation, colony formation, sphere formation, migration and invasive assays.
Results
From the TCGA database, the expression level of Dicer mRNA is increased in colorectal cancer; the level of Dicer protein is increased in oxaliplatin- or 5’FU-resistant cell lines. The drug resistant cells possess increased abilities in cell migration, invasion and sphere formation. Knocked-down expression of Dicer can enhance the drug sensitivity in drug resistant cells; in contrast, overexpression of Dicer increases drug resistance in parental drug sensitive cells. By next-generation sequencing and cDNA array, we found that the expression of a set of miRNAs and their downstream mRNAs is changed in oxaliplatin resistant cells. Dicer overexpression enhances the expression of those miRNAs and mRNAs in drug sensitive parental cells. Clinical evaluation further confirmed the increased expression of those miRNAs in the plasma of CRC patients is positively correlated with a poor response to oxaliplatin. In addition, NF-kB and Wnt pathways were found to be activated in drug resistant cells.
Conclusions
Our results suggest that those miRNAs may act as biomarkers to predict oxaliplatin response in colorectal cancer by detecting their plasma miRNAs. The molecular mechanism of those miRNAs in regulating the drug response is currently under our investigation.
Legal entity responsible for the study
The author.
Funding
Ministry of Science and Technology.
Disclosure
The author has declared no conflicts of interest.