scholarly journals Type and Gene Location of KIT Mutations Predict Progression-Free Survival to First-Line Imatinib in Gastrointestinal Stromal Tumors: A Look into the Exon

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 993
Author(s):  
Lorena Incorvaia ◽  
Daniele Fanale ◽  
Bruno Vincenzi ◽  
Ida De Luca ◽  
Tommaso Vincenzo Bartolotta ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Gene Location ◽  
Imatinib Treatment ◽  
Tumor Diameter ◽  
First Line ◽  
Free Survival ◽  
Metastatic Setting ◽  
Predictive Role ◽  
Exon 11

In previous studies on localized GISTs, KIT exon 11 deletions and mutations involving codons 557/558 showed an adverse prognostic influence on recurrence-free survival. In the metastatic setting, there are limited data on how mutation type and codon location might contribute to progression-free survival (PFS) variability to first-line imatinib treatment. We analyzed the type and gene location of KIT and PDGFRA mutations for 206 patients from a GIST System database prospectively collected at an Italian reference center between January 2005 and September 2020. By describing the mutational landscape, we focused on clinicopathological characteristics according to the critical mutations and investigated the predictive role of type and gene location of the KIT exon 11 mutations in metastatic patients treated with first-line imatinib. Our data showed a predictive impact of KIT exon 11 pathogenic variant on PFS to imatinib treatment: patients with deletion or insertion/deletion (delins) in 557/558 codons had a shorter PFS (median PFS: 24 months) compared to the patients with a deletion in other codons, or duplication/insertion/SNV (median PFS: 43 and 49 months, respectively) (p < 0.001). These results reached an independent value in the multivariate model, which showed that the absence of exon 11 deletions or delins 557/558, the female gender, primitive tumor diameter (≤5 cm) and polymorphonuclear leucocytosis (>7.5 109/L) were significant prognostic factors for longer PFS. Analysis of the predictive role of PDGFRA PVs showed no significant results. Our results also confirm the aggressive biology of 557/558 deletions/delins in the metastatic setting and allow for prediction at the baseline which GIST patients would develop resistance to first-line imatinib treatment earlier.

scholarly journals Early Tumor Shrinkage and Depth of Response Evaluation in Metastatic Pancreatic Cancer Treated with First Line Chemotherapy: An Observational Retrospective Cohort Study

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 939 ◽  
Author(s):  
Caterina Vivaldi ◽  
Lorenzo Fornaro ◽  
Carla Cappelli ◽  
Irene Pecora ◽  
Silvia Catanese ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Tumor Shrinkage ◽  
First Line ◽  
Free Survival ◽  
Depth Of Response ◽  
Early Tumor Shrinkage ◽  
Early Tumor

Early tumor shrinkage (ETS) and depth of response (DoR) predict favorable outcomes in metastatic colorectal cancer. We aim to evaluate their prognostic role in metastatic pancreatic cancer (PC) patients treated with first-line modified-FOLFIRINOX (FOLFOXIRI) or Gemcitabine + Nab-paclitaxel (GemNab). Hence, 138 patients were tested for ETS, defined as a ≥20% reduction in the sum of target lesions’ longest diameters (SLD) after 6–8 weeks from baseline, and DoR, i.e., the maximum percentage shrinkage in the SLD from baseline. Association of ETS and DoR with progression-free survival (PFS) and overall survival (OS) was assessed. ETS was reached in 49 patients (39.5% in the FOLFOXIRI, 29.8% in the GemNab group; p = 0.280). In the overall population, ETS was significantly associated with better PFS (8.0 vs. 4.8 months, p < 0.001) and OS (13.2 vs. 9.7 months, p = 0.001). Median DoR was −27.5% (−29.4% with FOLFOXIRI and −21.4% with GemNab, p = 0.016): DoR was significantly associated with better PFS (9.0 vs. 6.7 months, p < 0.001) and OS (14.3 vs. 11.1 months, p = 0.031). Multivariate analysis confirmed both ETS and DoR are independently associated with PFS and OS. In conclusion, our study added evidence on the role of ETS and DoR in the prediction of outcome of PC patients treated with first-line combination chemotherapy.

Progression-free survival in patients with cholangiocarcinoma with FGFR2 fusions or rearrangements: An exploration of response to systemic therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 588-588 ◽  
Author(s):  
Kristen Bibeau ◽  
Luis Féliz ◽  
Scott Barrett ◽  
Ling Na ◽  
Christine Francis Lihou ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Free Survival ◽  
Prior Therapy ◽  
First Line Therapy ◽  
Line Therapy

588 Background: Most cholangiocarcinoma (CCA) patients (pts) are diagnosed with advanced disease and are ineligible for surgery. FGFR2 fusions or rearrangements are present in 10–16% of pts with intrahepatic CCA (iCCA) and are reported to be oncogenic drivers. However, little data are available on the role of FGFR2 genetic alterations in the response to systemic cancer therapy. FIGHT-202 is a phase 2 study of pemigatinib (a selective, potent, oral FGFR1–3 inhibitor) in pts with previously treated advanced/metastatic CCA (NCT02924376); primary results were reported at ESMO 2019. FIGHT-202 enrolled pts who progressed on ≥1 prior therapy, allowing the examination of the role of FGFR2 alterations on the response to prior therapy. The objective of this post hoc analysis was to evaluate progression free survival (PFS) on standard systemic therapy received prior to study enrollment among pts with CCA harboring FGFR2 fusions or rearrangements ( FGFR2+). Methods: Case report forms were reviewed to determine disease history and exposure to prior lines of systemic cancer therapies (LOSCT) in the advanced setting before receiving pemigatinib. Only pts with sufficient data on prior LOSCT were included in this analysis. Median PFS was calculated using the Kaplan-Meier method. Results: 102 pts were included in this analysis (median age 54.5, 61.8% female). Median PFS on first-line therapy was 5.5 (95% CI: 4.0, 8.0) months. Among the 38 pts (37.3%) with ≥2 prior LOSCT, median PFS on second-line therapy was 4.4 (95% CI: 3.0, 5.3) months. Conclusions: This analysis provides data about PFS on standard systemic therapies for pts with FGFR2+ CCA. Median PFS on first-line therapy was lower than historical published data, and median PFS on second-line therapy was slightly longer than previously reported, in unselected CCA populations. Limitations of this analysis include retrospective examination of investigator reported data, and that clinical trial participants may not truly reflect a general CCA patient population. The short PFS on standard therapies in pts with FGFR2+ CCA highlights the need for development of other options including targeted therapies to improve outcomes.

Use of early tumor shrinkage as a response to VEGF inhibitors as a predictor of progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4631-4631 ◽  
Author(s):  
Viktor Gruenwald ◽  
Christoph Seidel ◽  
Martin Fenner ◽  
Michael Woike ◽  
Daniel Kalanovic
Keyword(s):  
Multivariate Analyses ◽  
Progression Free Survival ◽  
Tumor Shrinkage ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Early Tumor Shrinkage ◽  
Early Tumor ◽  
First Line Treatment

4631 Background: Several novel targeted agents significantly prolong overall survival (OS) in metastatic renal cell cancer (mRCC) patients (pts.). Translational research, however, has not identified any prospectively validated prognostic or predictive biomarkers. Recently, progression free survival (PFS), overall response rate (ORR) and early tumor shrinkage were proposed as putative predictors for clinical outcome. In this study we aim to explore the potential role of treatment induced tumor remission as a prognostic or predictive parameter in mRCC. Methods: In our analyses we investigated the putative prognostic role of best response according to RECIST 1.1 criteria (complete remission (CR), partial remission (PR), stable disease (SD), progressive disease (PD)) in first line Tyrosine-kinase inhibitor (TKI) treatment in n=83 pts. Responders were defined by achieving CR, PR or SD at any time during the course of treatment. Furthermore, we tested whether tumor shrinkage of 10% or more within 12 weeks of treatment qualifies as a potential cut-off-parameter to predict PFS or OS. Uni- and multivariate analyses were performed using Log-rang test, Kaplan-Meier-, and Cox-regression analysis. Results: Univariate analyses revealed that first-line treatment non-responders had a significantly shorter OS than responders (p <0.0001). Tumor shrinkage of <10% or ≥10% also correlated with an OS of 14.5 vs. 29.1 mo. (p=0.001) and a PFS of 3.0 vs. 11.5 mo. (p <0.001). In multivariate analyses tumor shrinkage of ≥10% was tested with other common variables such as ECOG, MSKCC-score, histology, and metastatic sites and proved to be a significant independent prognostic (HR 0.361; 95% CI 0.156-0.833) and predictive (HR 0.306; 95% CI 0.152-0.612) parameter. Conclusions: Our results outline that sensitivity to first line treatment of mRCC is an important prognostic factor in mRCC. Hereby tumor shrinkage of ≥10% within 12 weeks of treatment reveals a novel cut-off-parameter, which showed to be a promising prognostic and predictive marker in mRCC. Further investigations are needed to validate this parameter.

Use of HE4 and CA125 to predict surgical outcome and for prognostic value for progression-free survival (PFS) and overall survival (OS) in primary epithelial ovarian cancer (EOC) patients (pts).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5034-5034
Author(s):  
Ioana Braicu ◽  
Radoslav Chekerov ◽  
Rolf Richter ◽  
Ignace B. Vergote ◽  
Sven Mahner ◽  
...  
Keyword(s):  
Surgical Outcome ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Free Survival ◽  
Over Expression ◽  
Primary Epithelial Ovarian Cancer ◽  
Predictive Role ◽  
First Diagnosis

5034 Background: Optimal surgical cytoreduction and response to platinum (P) based chemotherapy (ChTh) remain the cornerstones of therapeutic management of primary EOC. Aim of this study was to analyze the predictive role of HE4 and CA125 as biomarkers (BM) for clinical outcome in primary EOC pts at diagnosis and during subsequent follow-up. Methods: In the European OVCAD project 275 pts with primary EOC were enrolled. Pts were eligible if radical cytoreductive surgery and P-based ChTh were applied. Plasma collected at first diagnosis and 6 months after 1st line ChTh in P-sensitive pts was analyzed for HE4 and CA125 levels using ELISA and Luminex technique, respectively. Results: Complete cytoreduction with no residual tumor disease (RTD) was obtained in 69.9% pts. HE4 and CA125 expression in plasma at first diagnosis correlated with RTD, p = 0.002 and p=0.002, respectively. The sensitivity (SE) and specificity (SP) of the combinative use of both BM in predicting RTD was 64.8% and 73.5%, respectively. Pts having over-expression of both BM in plasma had a 6.1 greater risk for RTD (p<0.001, OR: 6.107, 95% CI 2.41-15.46). P-resistance occurred more frequently when both BM were over-expressed (p=0.028, OR= 3.1, 95%CI 1.13-8.46). Elevated BM levels during follow-up predicted recurrence (SE 90% and SP 71% for CA125 ≥55U/ml; SE 72.7% and SP 81.4% for HE4 ≥150pM) and when HE4 or CA125 were positive, a SE of 86.4% and SP of 72.9% were achieved. Elevated CA125 and HE4 at 6 months following adjuvant therapy was associated with significantly poorer PFS (p<0.001, HR 9.6, 95%CI 3.93-23.44 with elevated HE4 or CA125, and HR=50.52, 95%CI 14.44-176.78, with elevated HE4 and CA125) and OS (p<0.001, HR=7.42 95%CI 1.43-38.42 with elevated HE4 or CA125 and HR=28.38 95%CI 6.50-123.97 with elevated HE4 and CA125). Conclusions: The combinative use of HE4 and CA125 appears to have a significant value in predicting optimal surgical outcome and development of P resistance disease in EOC pts. Elevated plasma levels 6 months after 1st line ChTh significantly correlate with OS and PFS in P-sensitive pts.

scholarly journals Amrubicin Monotherapy for Patients with Platinum-Refractory Gastroenteropancreatic Neuroendocrine Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Takayuki Ando ◽  
Ayumu Hosokawa ◽  
Hiroki Yoshita ◽  
Akira Ueda ◽  
Shinya Kajiura ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
First Line ◽  
Ki 67 ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Platinum Refractory ◽  
Grade 3

Objective. Patients with gastroenteropancreatic neuroendocrine carcinoma (NEC) have a poor prognosis. Platinum-based combination chemotherapy is commonly used as first-line treatment; however, the role of salvage chemotherapy remains unknown. This study aimed to analyze the efficacy and safety of amrubicin monotherapy in patients with platinum-refractory gastroenteropancreatic NEC.Methods. Among 22 patients with advanced gastroenteropancreatic NEC, 10 received amrubicin monotherapy between September 2007 and May 2014 after failure of platinum-based chemotherapy. The efficacy and toxicity of the treatment were analyzed retrospectively.Results. Eight males and two females (median age, 67 years (range, 52–78)) received platinum-based chemotherapy, including cisplatin plus irinotecan (n=7, 70%), cisplatin plus etoposide (n=2, 20%), and carboplatin plus etoposide (n=1, 10%) before amrubicin therapy. Median progression-free survival and overall survival after amrubicin therapy were 2.6 and 5.0 months, respectively. Two patients had partial response (20% response rate), and their PFS were 6.2 months and 6.3 months, respectively. Furthermore, NEC with response for amrubicin had characteristics with a high Ki-67 index and receipt of prior chemotherapy with cisplatin and irinotecan. Grade 3-4 neutropenia and anemia were observed in four and five patients, respectively.Conclusion. Amrubicin monotherapy appears to be potentially active and well-tolerated for platinum-refractory gastroenteropancreatic NEC.

scholarly journals Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma

Liver Cancer ◽  
2021 ◽  
pp. 1-10
Author(s):  
Petros Fessas ◽  
Muntaha Naeem ◽  
Matthias Pinter ◽  
Thomas U. Marron ◽  
David Szafron ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint Inhibitor ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Tumor Burden ◽  
Free Survival ◽  
Programmed Cell Death 1 ◽  
Predictive Role ◽  
Pugh Class

<b><i>Background and Rationale:</i></b> Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC. <b><i>Methods:</i></b> In a large international cohort of 450 ICI recipients from Europe, North America, and Asia, we categorized patients according to timing of ATB focusing on exposure within −30 to +30 days from ICI (early immunotherapy period [EIOP]). EIOP was evaluated in association with overall survival (OS), progression-free survival (PFS), and best radiologic response using RECIST 1.1 criteria. <b><i>Results:</i></b> Our study comprised mostly cirrhotic (329, 73.3%) males (355, 79.1%) with a Child-Turcotte Pugh class of A (332, 73.9%), receiving ICI after 1 therapy line (251, 55.9%) for HCC of Barcelona clinic liver cancer stage C (325, 72.4%). EIOP (<i>n</i> = 170, 37.9%) was independent of baseline clinicopathologic features of HCC and correlated with longer PFS (6.1 vs. 3.7 months, log-rank <i>p</i> = 0.0135). EIOP+ patients had similar OS, overall response, and disease control rates (DCRs) compared to EIOP. The effect of EIOP persisted in landmark time analyses and in multivariable models, confirming the independent predictive role of EIOP in influencing PFS following adjustment for covariates reflective of tumor burden, liver function, and ICI regimen administered. In patients receiving programmed cell death-1 receptor/ligand inhibitors monotherapy, EIOP was also associated with higher DCRs (61.4% vs. 50.9%, <i>p</i> = 0.0494). <b><i>Conclusions:</i></b> Unlike other oncological indications, ATB in the 30 days before or after ICI initiation is associated with improved benefit from immunotherapy, independent of disease and treatment-related features. Evaluation of the immune microbiologic determinants of response to ICI in HCC warrants further investigation.

PROX: Primary resistance to oxaliplatin containing regimen in the first line treatment of metastatic colorectal carcinoma—Retrospective analysis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 855-855
Author(s):  
Larissa Machado ◽  
Tiago Felismino ◽  
Diogo De Brito Sales ◽  
Diogo Morbeck ◽  
Amanda Karani ◽  
...  
Keyword(s):  
Chemotherapy Regimen ◽  
Progression Free Survival ◽  
First Line ◽  
Primary Resistance ◽  
Free Survival ◽  
Mucinous Component ◽  
First Response ◽  
Single Center Study ◽  
Third Line

855 Background: The rate of primary resistance to modern first line (FL) chemotherapy regimen in the treatment of metastatic colorectal cancer (mCRC) is low. Progression Disease (PD) to FOLFOX in the FL is less than 15% in most trials. Prognostic factors associated with worse outcome in mCRC have been identified. However, primary resistance to Oxaliplatin (PROX) containing regimen is not well understood, as well as the role of salvage therapy in further lines of treatment. The aim of the study was to analyze clinical and pathological characteristics of patients with PROX. Methods: A retrospective, single center study included patients that presented PD in the first response evaluation with an Oxaliplatin containing regimen in the FL treatment of mCRC. We also evaluated the Overall Survival (OS) and progression free survival (PFS) of these patients to second and third line. Clinical and pathological variables were analyzed and correlated with (OS). Results: A total of 55 patients were inclued. Median age these cohort was 57 years. Female/Male rate was 42%/58%. Mucinous component was 27%. Right and Left colon was 27% and 66%, respectively. BRAF mutation (2/16 pts). Wild type KRAS was 44%. Synchronic metastasis was 75%. Ressection of metastasis was performed in 20%. Liver limeted disease was found in 45%. Main chemotherapy regimen containing oxaliplatin was FOLFOX (78%) in first line. Bevacizumab, Cetuximab and Panitumumab were used in 21.8%, 9%, 1.8%, respectively. OS was 9.4 months. PFS in second line 3.8 months (47 pts) and third line 3.5 months (18 pts). The only variable associated with longer survival was resection of metastasis (25.6 x 8.6 months, p=0.039). Conclusions: No clinical and pathological variable were able to predict primary resistance to Oxaliplatin containing regimen. However, we found a higher proportion of mucinous subtype. Patients submitted to resection of metastasis had almost three fold the survival of patient that did not underwent surgery. Refractory patients have a very short survival. Further lines of treatment are not able to rescue these patients. Further studies focusing in patients with primary resistance to chemotherapy in first line are needed.

scholarly journals Neoadjuvant Trabectedin plus Radiotherapy in High-Grade Sarcoma of the Leg: A Case Report

2018 ◽  
Vol 11 (2) ◽  
pp. 499-504
Author(s):  
António José Loureiro da Silva ◽  
Carolina Carvalho ◽  
Miguel Jacobetty ◽  
João Freitas ◽  
Ruben Fonseca ◽  
...  
Keyword(s):  
Spindle Cell ◽  
Progression Free Survival ◽  
Spindle Cell Sarcoma ◽  
First Line ◽  
Free Survival ◽  
High Grade Sarcoma ◽  
The Right ◽  
Disease Free ◽  
Line Chemotherapy

Here, we present the case of a 78-year-old male patient with undifferentiated spindle cell sarcoma on the posteromedial surface of the right leg who experienced a long-lasting progression-free survival. Due to an underlying cardiac disease, the patient was not suitable for anthracyclines. In September 2015, he received first-line chemotherapy with trabectedin (Yondelis®) at the approved dosage and regimen – concomitant with external radiotherapy (RT). After the first 9 cycles of trabectedin plus RT given in the neoadjuvant setting, the patient underwent surgical resection. At that stage, we observed a very good pathological response with 80% of necrotic area. The patient resumed the therapy with trabectedin; however, approximately 5 months later, we observed a new nodular heterogeneous lesion with ill-defined margins in the right leg and suggestive of tumor relapse. Subsequently an above-the-knee amputation was performed, and the patient resumed his trabectedin therapy with the same dosage and regimen. In January 2018, almost 2 1/2 years after the start of trabectedin treatment and 30+ cycles of trabectedin, the patient is locoregionally and distant metastatically disease-free. Currently, the treatment with trabectedin is maintained without any significant serious toxicity. Future clinical trials are needed to gain additional insights into the role of trabectedin maintenance therapy until disease progression in the neoadjuvant setting and to identify predictive and prognostic criteria for response to trabectedin in patients with advanced sarcoma.

Liver metastases as predictors of outcome in renal cell carcinoma (RCC) patients (pts) treated with first-line sunitinib (SU) and sorafenib (SO).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 536-536
Author(s):  
Paolo Grassi ◽  
Elena Verzoni ◽  
Luca Porcu ◽  
Isabella Testa ◽  
Roberto Iacovelli ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
First Line ◽  
Duration Of Treatment ◽  
Risk Of Death ◽  
Product Limit ◽  
Predictive Role ◽  
Metastatic Sites

536 Background: The predictive role of metastatic sites in RCC pts treated with tyrosine kinase inhibitors (TKIs) is unclear. Aim of this study was to investigate whether first line SU and SO was associated to metastatic sites in terms of progression-free survival (PFS) and overall survival (OS). Methods: A retrospective cohort of consecutive metastatic RCC (mRCC) pts treated with TKIs at Istituto Nazionale Tumori of Milan was analyzed. All pts received at least one targeted therapy including: SO, SU, bevacizumab plus interferon-alfa, pazopanib or temsirolimus. The product limit method was used to estimate survival functions and Cox regression to estimate hazard ratios (HRs) and to test statistical interaction between sub-groups identified by different metastatic sites. Results: 358 mRCC pts receiving first line TKIs between January 2005 and October 2012 were evaluated. Overall 206 pts (58%) received SO while 103 pts (29%) SU. Median duration of treatment for SU and SO groups was 16 (95%CI 12.0-20.1) and 9 months (mo) respectively (95%CI 7.0-12.0). After a median follow-up of 56.1 mo (range: 1.0-93.2) median OS for SO group was 19.9 mo (95%CI 16.0-25.1) while OS for SU group was not yet defined. Noteworthy 142 pts (69%) treated with SO received SU at disease progression (PD) while 36 pts (35%) received SO at SU failure. A statistically significant interaction between first line treatment and metastatic sites was found for the liver site in terms of PFS and OS (PFS p=0.034; OS p=0.004). SU was associated with a 18% [95%CI (-37%)- 123%] higher risk of PD as compared to SO in pts with liver mets while pts without liver mets showed a 46% [95%CI (-61%)-(-24%)] decreased risk of PD as compared to SO. SU was associated with a 40% [95%CI (-32%)-187%] higher risk of death as compared to SO in pts with liver mets while pts without liver mets showed a 62% [95%CI (-76%)-(-40%)] decreased risk of death as compared to SO. The predictive role of liver mets was confirmed introducing the Motzer score (PFS p=0.084; OS p=0.009). Conclusions: mRCC pts with liver mets treated with first line SO showed a better outcome as compared to SU while pts without liver mets treated with first line SO showed a worse outcome as compared to SU.

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