Genomic overview of right-sided and left-sided colorectal cancer using comprehensive genomic sequencing.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15101-e15101
Author(s):  
Yoshifumi Shimada ◽  
Hitoshi Kameyama ◽  
Masayuki Nagahashi ◽  
Hiroshi Ichikawa ◽  
Ryoma Yagi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Pi3k Pathway ◽  
Genetic Alterations ◽  
Genomic Sequencing ◽  
Wild Type ◽  
Mutant Type ◽  
The Difference ◽  
Gene Alterations

e15101 Background: Although the difference in right vs. left sidedness of colorectal cancer (CRC) in response to targeted therapy has been reported, we hypothesized that right-sided colorectal cancer (RCC) is more likely to have genetic alterations associated with resistance of anti-EGFR therapy. We tested this hypothesis using comprehensive genomic sequencing (CGS) on a set of samples from well-characterized CRC patients. Methods: Two-hundred-one primary colon cancer patients with either RCC or left-sided colorectal cancer (LCC) were analyzed. We investigated gene alterations using 415 gene panel, which includes the gene alterations associated with resistance of anti-EGFR therapy: TK receptors ( ERBB2, MET, EGFR, FGFR1, and PDGFRA), RAS pathway ( KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and PI3K pathway ( PTEN and PIK3CA). We defined the patients who had no alterations in any of the genes as “all wild-type”, who are theoretically considered as responders of anti-EGFR therapy. Other patients with genetic alterations in resistance pathways were defined as “mutant-type”. Results: Fifty-six patients (28%) and 145 patients (72%) had RCC and LCC, respectively. Mutation of PIK3CA, BRAF, ACVR2A, MSH6, and CTNNB1 were significantly associated with RCC. Conversely, mutation of APC and TP53 were significantly associated with LCC. Regarding the gene alterations associated with anti-EGFR therapy, only 6 of 56 patients (11%) of RCC were “all wild-type”; in contrast to 41 of 145 patients (28%) of LCC that were “all wild-type” ( P = 0.009). In 45 Stage IV patients treated with anti-EGFR therapy, RCC showed significantly worse progression-free survival (PFS) than LCC ( P = 0.019), and “mutant-type” RCC showed worse PFS compared to the others ( P = 0.018). Conclusions: RCC is more likely to have the genetic alterations associated with resistance of anti-EGFR therapy compared to LCC. Primary tumor sidedness is a surrogate for the non-random distribution of molecular subtypes in CRC.

scholarly journals Genomic Profiling of KRAS/NRAS/BRAF/PIK3CA Wild-Type Metastatic Colorectal Cancer Patients Reveals Novel Mutations in Genes Potentially Associated with Resistance to Anti-EGFR Agents

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 859 ◽  
Author(s):  
Anna Maria Rachiglio ◽  
Matilde Lambiase ◽  
Francesca Fenizia ◽  
Cristin Roma ◽  
Claudia Cardone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
De Novo ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Copy Number Variations ◽  
Wild Type ◽  
Single Nucleotide Variants ◽  
Colorectal Cancer Patients ◽  
De Novo Resistance

Previous findings suggest that metastatic colorectal carcinoma (mCRC) patients with KRAS/NRAS/BRAF/PIK3CA wild-type (quadruple-wt) tumors are highly sensitive to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs). However, additional molecular alterations might be involved in the de novo resistance to these drugs. We performed a comprehensive molecular profiling of 21 quadruple-wt tumors from mCRC patients enrolled in the “Cetuximab After Progression in KRAS wild-type colorectal cancer patients” (CAPRI-GOIM) trial of first line FOLFIRI plus cetuximab. Tumor samples were analyzed with a targeted sequencing panel covering single nucleotide variants (SNVs), insertions/deletions (Indels), copy number variations (CNVs), and gene fusions in 143 cancer-related genes. The analysis revealed in all 21 patients the presence of at least one SNV/Indel and in 10/21 cases (48%) the presence of at least one CNV. Furthermore, 17/21 (81%) patients had co-existing SNVs/Indels in different genes. Quadruple-wt mCRC from patients with the shorter progression free survival (PFS) were enriched with peculiar genetic alterations in KRAS, FBXW7, MAP2K1, and NF1 genes as compared with patients with longer PFS. These data suggest that a wide genetic profiling of quadruple-wt mCRC patients might help to identify novel markers of de novo resistance to anti-EGFR MoAbs.

scholarly journals Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study

2021 ◽  
Author(s):  
Takeshi Kato ◽  
Yoshinori Kagawa ◽  
Yasutoshi Kuboki ◽  
Makio Gamoh ◽  
Yoshito Komatsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Therapeutic Option ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Wild Type ◽  
Open Label ◽  
Safety And Efficacy ◽  
Multicentre Phase

Abstract Background We aimed to assess the safety and efficacy of combination treatment with panitumumab plus trifluridine/tipiracil (FTD/TPI) in patients with wild-type RAS metastatic colorectal cancer (mCRC) who were refractory/intolerant to standard therapies other than anti-epidermal growth factor receptor therapy. Methods APOLLON was an open-label, multicentre, phase 1/2 trial. In the phase 1 part, 3 + 3 de-escalation design was used to investigate the recommended phase 2 dose (RP2D); all patients in the phase 2 part received the RP2D. The primary endpoint was investigator-assessed progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and safety. Results Fifty-six patients were enrolled (phase 1, n = 7; phase 2, n = 49) at 25 Japanese centres. No dose-limiting toxicities were observed in patients receiving panitumumab (6 mg/kg every 2 weeks) plus FTD/TPI (35 mg/m2 twice daily; days 1–5 and 8–12 in a 28-day cycle), which became RP2D. PFS rate at 6 months was 33.3% (90% confidence interval [CI] 22.8–45.3). Median PFS, OS, ORR, DCR, and TTF were 5.8 months (95% CI 4.5–6.5), 14.1 months (95% CI 12.2–19.3), 37.0% (95% CI 24.3–51.3), 81.5% (95% CI 68.6–90.8), and 5.8 months (95% CI 4.29–6.21), respectively. Neutrophil count decreased (47.3%) was the most common Grade 3/4 treatment-emergent adverse event. No treatment-related deaths occurred. Conclusion Panitumumab plus FTD/TPI exhibited favourable anti-tumour activity with a manageable safety profile and may be a therapeutic option for pre-treated mCRC patients.

Evaluation Changes in Indicators of Oncological Service in Colorectal Cancer in East Kazakhstan Region

2021 ◽  
Vol 9-10 (219-220) ◽  
pp. 11-16
Author(s):  
Yerkezhan Zhadykova ◽  
◽  
Sauirbay Sakhanov ◽  
Dulat Turebayev ◽  
Dariyana Kulmirzayeva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mortality Rate ◽  
Early Diagnosis ◽  
Stage Iv ◽  
International Agency ◽  
Keywords Colorectal Cancer ◽  
Anti Cancer ◽  
East Kazakhstan ◽  
The Difference ◽  
The Republic

About 3.15 million new cases of colorectal cancer (CRC) are predicted and it is expected that about 1.62 million human will die from this pathology, according to the forecasts of the International Agency for Research on Cancer in 2040. To this aim, an analysis studying studying the indicators of the oncological service for CRC also makes it possible to evaluate the ongoing anti-cancer measures in East Kazakhstan region. Aim. Evaluate some indicators of the oncological service at CRC in East Kazakhstan region in 2009 to 2018. Materials and methods. The research material was data from the Ministry of Health of the Republic of Kazakhstan – annual form No. 7 and 35 regarding CRC (ICD 10 – C18-21) for 2009-2018 in East Kazakhstan region – incidence, mortality, early diagnosis, neglect, morphological verification. A retrospective study using descriptive and analytical methods of biomedical statistics was used as the main method. Results and discussion. For 2009-2018, 3,661 new cases of CRC were registered in East Kazakhstan region for the first time. The incidence of CRC was 25.30/0000 and in dynamics tended to increase from 21.90/0000 (2009) to 25.70/0000 in 2018, the difference was statistically significant (t=1.99 and p=0.047). The mortality rate from CRC tended to decrease from 15.50/0000 to 14.70/0000 (p=0.591), and the average annual mortality rate from CRC was 15.60/0000. The indicators of early diagnosis (the proportion of patients with stage I-II) improved from 58.8% (2009) to 62.3% in 2018, and, accordingly, the indicators of the proportion of neglected patients significantly decreased with stage III (from 25.5% to 20.8%), while with stage IV (from 15.7% to 16.9%) there is a slight increase. The indicators of morphological verification in CRC improved from 90.5% to 98.6% during the studied years. Conclusion. An improvement in the indicators of morphological verification and early diagnosis of CRC was found. The obtained results are recommended to be used for monitoring anti-cancer measures in the region. Keywords: colorectal cancer, incidence, mortality, early diagnosis, neglect, morphological verification.

Tumor bulk as a prognostic biomarker and predictor of benefit from anti-EGFR therapy in patients with metastatic colorectal cancer: Analysis of 476 patients from the ARCAD Clinical Trials Program.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 108-108
Author(s):  
Benjamin Adam Weinberg ◽  
Manel Rakez ◽  
Benoist Chibaudel ◽  
Tim Maughan ◽  
Richard Adams ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Lung Metastases ◽  
Performance Status ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Wild Type ◽  
Cox Models ◽  
Study Results

108 Background: Primary tumor sidedness has emerged as a prognostic and predictive biomarker for patients (pts) with metastatic colorectal cancer (mCRC). Tumor bulk has also been postulated to predict response to anti-EGFR therapy. We sought to evaluate the role of tumor bulk as a predictive biomarker to anti-EGFR therapy in pts with left- (LS) and right-sided (RS) mCRC. Methods: Data from 476 pts with mCRC enrolled across 2 first-line trials of anti-EGFR plus chemotherapy versus chemotherapy were pooled. Pts were included if there was available information on tumor sidedness and tumor bulk. All were KRAS wild-type and BRAF wild-type or unknown BRAF status. The right colon was defined as the cecum through the transverse colon, and the left colon as the splenic flexure through the rectum. Tumor bulk was the mean tumor size of target lesions at baseline, bulky defined as > 3.5 cm. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for performance status (PS), platelet count, primary tumor (PT) resection, number of metastatic sites, and stratified by study. Results: Pts with bulky tumors (211, 44%) had higher PS, white blood cell and platelet counts, higher CEA, fewer sites of metastatic disease, more liver than lung metastases, and fewer had PT resection. OS and PFS medians in months (mos) are presented in the table with 95% confidence intervals (95%CIs). Bulky tumors had inferior median OS compared with non-bulky (mOS, 17.9 vs. 21.3 mos, HRadj 1.33, 95% CI 1.05-1.69, P = 0.016) although median PFS was similar (mPFS, 8.6 vs. 8.7 mos, HRadj 1.15, 95% CI 0.92-1.42, P = 0.21). Conclusions: Tumor bulk is an independent prognostic factor for OS in KRAS wild-type and BRAF wild-type or unknown BRAF status pts. Pts with non-bulky RS tumors have survival outcomes similar to pts with bulky LS tumors. Although the mPFS for pts with RS tumors treated with anti-EGFR therapy was the lowest across subgroups, this finding was not statistically significant. Further research is warranted into whether pts with bulky RS tumors benefit from anti-EGFR therapy. Clinical trial information: NCT00182715, NCT00640081. [Table: see text]

scholarly journals Randomized Phase II Study of SOX+B-mab Versus SOX+C-mab in Patients With Previously Untreated Recurrent Advanced Colorectal Cancer With Wild-Type KRAS (MCSGO-1107 Study)

2021 ◽  
Author(s):  
Yujiro Nishizawa ◽  
Naotsugu Haraguchi ◽  
Hirotoshi Kim ◽  
Yoshihito Ide ◽  
Ken Nakata ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Wild Type ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Early Tumor ◽  
Patient Prognosis ◽  
Clinical Trials Registry

Abstract Background: Although chemotherapy for metastatic colorectal cancer (mCRC) has improved, the standard chemotherapy regimens for patients with RAS wild-type mCRC remain debated.Methods: This randomized phase II, open-label, multicenter study compared the efficacy and safety of S-1 and oxaliplatin (SOX)+bevacizumab (B-mab) with SOX+cetuximab (C-mab) in patients with previously untreated recurrent advanced CRC with wild-type KRAS. Between February 2012 and October 2016, 45 patients were enrolled.Results: Overall response rates were 59.1% and 43.5% (p=0.29) and disease control rates were 90.9% and 91.3% (p=0.96) in the SOX+B-mab and SOX+C-mab groups, respectively. Median overall survival (OS) was 25.3 and 15.5 months (HR=0.607, p=0.167) and median progression-free survival (PFS) were 11.7 and 5.5 months (HR=0.558, p=0.077) in the SOX+B-mab and SOX+C-mab groups, respectively. The OS and PFS of patients with early tumor shrinkage (ETS) were not significantly different in the SOX+B-mab group. However, they were significantly better when ETS was ≥20 in the SOX+C-mab group (p=0.032 and p=0.003, respectively).Conclusions: The efficacy and safety of SOX+B-mab and SOX+C-mab for wild-type KRAS recurrent advanced CRC as first-line chemotherapy were almost the same. Consideration of the treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen.Trial registration: UMIN Clinical Trials Registry (UMIN000006706)Date of registration: NOV/11/2011URL of trial registry record:https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007920

Abdominal desmoid- course, unique genetic background, and severe outcomes in a large local series.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23544-e23544
Author(s):  
Ophir Gilad ◽  
Ophir Gilad ◽  
Hana Strul ◽  
Guy Rosner ◽  
Nathan Gluck ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Cord Compression ◽  
Genetic Alterations ◽  
Mortality Data ◽  
Cox Inhibitors ◽  
Treatment Regimens ◽  
Cancer Related Gene ◽  
Surgical History ◽  
Gene Alterations

e23544 Background: Abdominal desmoid tumors are locally aggressive, non-metastatic tumors that develop mainly in Familial adenomatous polyposis (FAP) patients, within the mesentery or abdominal wall. Understanding and implications of treatment regimens are evolving. We aimed to assess course, treatment and outcomes of FAP and non-FAP abdominal desmoids and their related genetic alterations. Methods: Retrospective cohort study. Demographics, tumor characteristics, oncological and surgical history, complications, genetic-testing and mortality data were retrieved from two tertiary referral centers. Results: Sixty-two patients were identified (46 FAP, 16 non-FAP) with a median follow up of 72.4 months. Thirty-eight patients (61.3%) underwent surgical procedures: twelve urgent and 26 elective. Out of 33 tumor resections, 39.4% recurred. Hormonal therapy, COX-inhibitors, chemotherapy, imatinib and sorafenib were used in 35(56.4%), 30(48.4%), 18(29.1%), 7(11.3%) and 8(12.9%) of patients, respectively, with 2 years progression-free survival of 67.8%, 57.7%, 38.4%, 28.5%, respectively. Only 1/9 patients treated with sorafenib had disease progression after a median follow up of 6.8 months. Forty-one patients (66.1%) suffered complications: bowel obstruction (30.6%), hyperalimentation (14.5%), ureteral obstruction (12.9%), perforation (11.3%), abscess formation (3.2%) and spinal cord compression (3.2%). Two patients died. Non-FAP patients presented with three renal-cell carcinomas and one germ-cell tumor and carried pathogenic mutations in CHEK2, BLM, ERCC5, MSH6 and PALB2. Conclusions: Abdominal desmoids are mostly FAP-related and are associated with severe outcomes. We report a group of non-FAP abdominal desmoids that includes patients with additional cancer-related gene alterations. This interesting group should undergo genetic consultation and be further explored.

Evaluation of different MET genotypes as biomarkers for immunotherapy outcomes in NSCLC patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21032-e21032
Author(s):  
Xuanzong Li ◽  
Linlin Wang
Keyword(s):  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Rank Test ◽  
Wild Type ◽  
Exact Test ◽  
Entire Cohort ◽  
Kaplan Meier ◽  
Tumor Mutational Burden ◽  
The Difference ◽  
Nsclc Patients

e21032 Background: Previous studies suggested that MET exon 14 ( METex14) mutation regarding as a distinct subset was sensitive to MET-inhibitors, but poorly response to immunotherapy. Conversly, MET non-exon-14 (non-ex14) mutations including those undetermined functions and affecting the kinase or extracellular domains were found to be associated with the resistance to MET-inhibitors. However, therapeutic strategies for MET-non-ex14 mutant cancer are still largely unknown, and the relationship between MET-non-ex14 mutations and the efficacy of immune checkpoint inhibitors (ICIs) has never been reported. Using two public ICIs-treated cohorts, we aimed to assess the role of MET mutations including both METex14 and MET-non-ex14 mutations in NSCLC patients undergoing ICIs therapy. Methods: A total of 385 ICIs-treated NSCLC patients were enrolled to our study. MET mutations were defined as any nonsynonymous mutations, and we divided them into METex14 and MET-non-ex14 mutation subsets according to the mutated-position on MET. Kruskal-Wallis test was used to analyze the difference of tumor mutational burden (TMB) score, and the Fisher’s exact test was applied to compare the rates of durable clinical benefit (DCB). Log-rank test was used to analyze the differences between Kaplan-Meier survival curves. Results: In the entire cohort, we found that 17 patients (17/385, 4.4%) had MET mutations, most of which were pure METex14 mutations (10/17, 58.8%). The median TMB of patients in the entire NSCLC cohort was 6.89 mut/Mb. MET-non-ex14 mutant patients (7/385, 1.8%) possessed a significantly higher TMB than METex14-mutant (10/385, 2.6%) and MET wild-type (368/385, 95.6%) sub-cohorts, respectively (median TMB, 17.92 mut/Mb versus 4.17 mut/Mb, p = 0.008; 17.92 mut/Mb versus 6.96 mut/Mb, p = 0.01, respectively). DCB was more common in patients harbored MET-non-ex14 mutations than patients with METex14 mutations and MET wild-type (66.7% versus 14.3%, p = 0.103; 66.7% versus 29.9%, p = 0.075, respectively). We found that patients with MET-non-ex14 mutations had a numerically longer progression free survival (PFS) than those with METex14 mutations and MET wild-type (p = 0.169). Moreover, the PFS was significantly longer in MET-non-ex14-mutant subgroup than patients with METex14 mutations (median PFS, 9.1 versus 2.1 months, p = 0.025). Correspondingly, the overall survival (OS) was significantly longer in MET-non-ex14-mutant subgroup than their wild-type counterparts (median OS, not reached versus 11 months, p = 0.039). Additionally, patients with MET-non-ex14 mutations exhibited relatively better OS versus METex14-mutant patients (median OS, not reached versus 18 months, p = 0.175). Conclusions: MET-non-ex14 mutations were associated with higher TMB, improved DCB rate, and could act as a favorable prognostic biomarker in ICIs-treated NSCLC patients.

scholarly journals Cetuximab versus bevacizumab maintenance following prior 8-cycle modified FOLFOXIRI plus cetuximab in Asian postmenopausal women with treatment-naive KRAS and BRAF wild-type metastatic colorectal cancer

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052093044
Author(s):  
Baomin Chen ◽  
Donghua Zheng ◽  
Weiguang Yu ◽  
Cuiping Huang ◽  
Junxing Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Postmenopausal Women ◽  
Induction Therapy ◽  
Maintenance Treatment ◽  
Progression Free Survival ◽  
Wild Type ◽  
Clinical Endpoints ◽  
Treatment Naïve

Objective To assess the efficacy and safety of cetuximab (CE) versus bevacizumab (BE) maintenance treatment after prior 8-cycle modified 5-fluorouracil, folinate, oxaliplatin, and irinotecan (FOLFOXIRI) plus CE induction therapy in treatment-naive KRAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC). Methods From 2012 to 2017, prospectively maintained databases were reviewed to assess Asian postmenopausal women with treatment-naive KRAS and BRAF wt mCRC who underwent modified FOLFOXIRI plus CE induction therapy, followed by CE or BE maintenance until disease progression or death. Co-primary clinical endpoints were progression-free survival (PFS) and overall survival (OS). Results A total of 222 women were included (CE n = 110 and BE n = 112). At a median follow-up of 27.0 months (interquartile range, 6.5–38.6 months), median PFS was 21.9 months (95% confidence interval [CI] 16.4–24.4) and 17.7 months (95% CI 11.3–19.0) for CE and BE groups, respectively (hazard ratio [HR] 0.31, 95% CI 0.15–0.46); median OS was 26.0 months (95% CI 23.4–28.7) and 22.7 months (95% CI 21.2–24.3) for CE and BE groups, respectively (HR 0.22, 95% CI 0.11–0.37). Conclusions CE maintenance treatment is more poorly tolerated but has a slightly more modest survival benefit compared with BE maintenance treatment in mCRC.

scholarly journals P14.95 Is the pathological-grade relevant in “IDH-wild type, TERT-mutant” diffuse-gliomas? An analysis in 147 patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii90-iii90
Author(s):  
A E Danyeli ◽  
C B Akyerli ◽  
A Dinçer ◽  
E Coşgun ◽  
U Abacıoğlu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Lower Grade ◽  
Wild Type ◽  
Ki 67 ◽  
Who Grade ◽  
Free Survival ◽  
Tert Promoter ◽  
Diffuse Gliomas

Abstract BACKGROUND Although the word “glioblastoma” still denotes a grade-IV pathology, basic molecular studies have clearly indicated that a significant proportion of lower-grade gliomas harbor genetic alterations typical of glioblastomas. Based on these findings cIMPACT-NOW update 3 has defined an entity called the “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. A TERT-promoter mutation is one of these typical molecular markers of glioblastomas. In this study we analyzed IDH-wild type, TERT-mutant diffuse gliomas of different pathological grades to look for differences in demographic, clinical and survival characteristics. MATERIAL AND METHODS 147 adult hemispheric diffuse-gliomas with wild-type IDH1/2 and mutant TERT-promoter (C228T or C250T) were retrospectively analyzed. Primary thalamic, cerebellar brainstem or spinal cases were excluded. 126 (86%), 16(11%) and 5(3%) patients were WHO grade IV, III and II respectively. After surgical treatment or stereotactic biopsy all patients underwent chemoradiation. Median follow-up was 16mo (1–110). Tumors of different grades were compared for age, gender, multifocality, gliomatosis pattern, Ki-67 index, progression-free survival and overall-survival. RESULTS Mean age at presentation for grade II, III and IV were comparable (58.1, 58 and 58.1; ANOVA, p=0.72). There was a slight male predominance in both lower-grades and WHO-grade IV (M:F ratios 1.625 and 1.74). Mean Ki-67 index was significantly higher in higher grades (0.06, 0.14 and 0.25 for grades II, III and IV; ANOVA, p=0.001). Multifocality was comparable (chi-sq, p=1) in lower-grades (3/21; 14.3%) vs. WHO-grade IV (18/126; 14.3%). Gliomatosis pattern was comparable (chi-sq, p=0.095) in lower-grades (2/21; 9.5%) vs. (3/126; 2.3%). Median recurrence free survival (RFS) was 16 months (0–63) in lower-grades and 8months (1–50) in WHO-grade IV. PFS was significantly different between 3 WHO-grades (Log rank, p=0.007) and also between lower-grades and WHO-grade IV (Log rank, p=0.002). Median overall survival was 26 months(2–110) in lower-grades and 15mo(1–91) in WHO-grade IV. OS was significantly different between 3 WHO-grades (Log rank, p=0.014) and also between lower-grades and WHO-grade IV (Log rank, p=0.007). CONCLUSION Increasing pathological grades of hemispheric “IDH-wild type, TERT-mutant diffuse gliomas” have similar demographic and clinical characteristics but incrasing proliferation indices, decrasing progression free survival and shorter overall survival. The findings may be suggesitve of different grades of one common tumor entity.

Erdafitinib: A novel therapy for FGFR-mutated urothelial cancer

2020 ◽  
Vol 77 (5) ◽  
pp. 346-351 ◽  
Author(s):  
Kiera Roubal ◽  
Zin W Myint ◽  
Jill M Kolesar
Keyword(s):  
Bladder Cancer ◽  
Urothelial Cancer ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Clinical Effectiveness ◽  
Genetic Alterations ◽  
Novel Therapy ◽  
Days Of Therapy ◽  
Phase 2 Clinical Trial ◽  
Gene Alterations

Abstract Purpose To provide an overview of fibroblast growth factor receptor (FGFR) gene alterations and the pharmacology, clinical effectiveness, dosage and administration, cost, and place in therapy of erdafitinib in bladder cancer. Summary Erdafitinib (Balversa, Janssen Pharmaceuticals) is a novel pan-FGFR inhibitor recently approved for the treatment of patients with advanced urothelial cancer with specific FGFR genetic alterations who have received at least one prior platinum-containing regimen. Erdafitinib binding to the FGFR2 and FGFR3 receptors inhibits FGF activity, resulting in cell death. Erdafitinib is available in tablet form, and the current recommended daily dosing is 8 mg, with dose escalation to 9 mg after 14 to 21 days of therapy if tolerated. A phase 2 clinical trial demonstrated that patients who received erdafitinib experienced on average 5.5 months of progression-free survival (95% confidence interval [CI], 4.2-6.0 months). In addition, 40% (95% CI, 31-50%) of patients responded to erdafitinib therapy. Patients receiving erdafitinib therapy should be monitored specifically for elevations in serum phosphate levels and changes in vision. Other adverse effects include anemia, thrombocytopenia, and electrolyte abnormalities. Conclusion Erdafitinib is the first small-molecule FGFR inhibitor approved for use in advanced bladder cancer.

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