Impact of tumor location on effectiveness of first-line 5-FU-based palliative doublet chemotherapy in patients with metastatic gastroesophageal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 240-240
Author(s):  
Suleyman Yasin Goksu ◽  
Rodrigo Alterio ◽  
Elizabeth McGehee ◽  
Muhammad Shaalan Beg ◽  
Syed Mohammad Ali Kazmi ◽  
...  
Keyword(s):  
Peritoneal Metastasis ◽  
Primary Tumor ◽  
Palliative Chemotherapy ◽  
Progression Free Survival ◽  
Safety Net ◽  
Tumor Location ◽  
Molecular Characteristics ◽  
First Line ◽  
Free Survival ◽  
Doublet Chemotherapy

240 Background: While gastroesophageal cancers with different primary tumor locations can have distinct molecular characteristics and clinical outcomes, the efficacy of palliative chemotherapy in tumors with different locations is unknown. Using primary tumor location as a surrogate for molecular subtype, we investigated the differential efficacy of first-line doublet chemotherapy in metastatic gastroesophageal adenocarcinomas. Methods: We performed a retrospective review of patients with metastatic gastroesophageal adenocarcinoma who received first-line palliative chemotherapy at the University of Texas Southwestern Medical Center and the Dallas County Safety Net Parkland Hospital diagnosed between 2011-2019. Cases were identified using cancer registries. We categorized the tumor location as proximal or distal based on endoscopy and imaging studies. Disease response was assessed on the first staging scan and classified as ‘disease shrinkage, stability, or progression.’ Overall and progression-free survival were evaluated using Kaplan-Meier and Cox proportional hazards methods. Results: 99 patients were identified; 58.6% had proximal tumors. Patients with proximal tumors were more likely to be white (38% vs. 13%, p = 0.008) and older with age ≥ 50 years (71% vs. 51%, p = 0.04) and less likely to have peritoneal metastasis (48% vs. 78%, p = 0.003) than distal tumors. Patients with proximal tumors had a higher disease shrinkage than patients with distal tumors (53% vs. 21%, p = 0.004). Patients with proximal tumors also had better overall survival (median 12.5 vs. 8.7 months) and progression-free survival in response to 5-FU based chemotherapy (median 5 vs. 4 months) compared to patients with distal tumors, but this was not statistically significant. On multivariable analysis, tumor location was not independently predictive of progression-free survival after adjusting for age, gender, presence of signet rings, diffuse, intestinal histology, and peritoneal metastasis (HR 1.22 95% CI 0.74-2.00), but pretreatment albumin was (HR 0.63 95% CI 0.43-0.94). Conclusions: Proximal gastroesophageal cancers have a better clinical response to first-line 5FU containing chemotherapy than distal cancers. Currently, there is no platform to determine molecular subgroups that is commercially available. Until testing for this becomes available, differences in response rates to palliative chemotherapy in gastroesophageal cancers with different anatomical locations should be recognized and studied further.

Real-world outcomes in pancreatic adenocarcinoma (PDAC) and persona types with implications for standard of care (SOC) therapy (Tx).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 735-735
Author(s):  
Emanuel Petricoin ◽  
Michael J. Pishvaian ◽  
Patricia DeArbeloa ◽  
Daniel Barg ◽  
Dzung Thach ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Standard Of Care ◽  
Tumor Board ◽  
Molecular Characteristics ◽  
First Line ◽  
Free Survival ◽  
Longitudinal Outcomes ◽  
Molecular Alterations ◽  
Deficiency Type ◽  
Improve Patient

735 Background: Molecular profiling (MP) for PDAC has gained increased acceptance and we previously demonstrated that targeting actionable mutations can improve patient (pt) outcomes. However, the correlations of diverse patterns of molecular alterations with outcomes following SOC Tx are largely unknown. Methods: We analyzed longitudinal outcomes of 1355 PDAC pts who underwent MP and received SOC Tx. “Persona” types were established based on the molecular characteristics of each pt using unsupervised clustering, as well as a supervised review defined by our molecular tumor board, following classifications reported in previous studies. Progression-free survival (PFS) for each type was assessed based on the choice of first-line Tx (i.e. FOLFIRINOX [FFX] vs. gemcitabine + nab-paclitaxel [GA]). Statistical comparisons were made against all other types within a specific Tx group. Results: The prognostic/predictive value of the persona types for 1st-line Tx revealed distinct differences in outcomes (Table). As expected, the DDR deficiency type was associated with a significantly improved PFS for pts treated with FFX but not for GA. In addition, pts in the cell cycle type had a worse PFS compared to other persona types for both FFX and GA. Using this platform, we will further subdivide the persona types into molecular subtypes and associate these with pt outcomes. Conclusions: Our analyses demonstrate that specific molecular persona types exist in PDAC pts and can be linked to Tx outcomes. Ultimately, knowing the persona type/subtype early in a pt’s Tx course may help personalize Tx to improve outcomes. [Table: see text]

Prognostic impact of primary tumor location on survival time in patients (pts) with metastatic colorectal cancer (mCRC) treated with cetuximab plus oxaliplatin-based chemotherapy: A subgroup analysis of the JACCRO CC-05/06.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 613-613 ◽  
Author(s):  
Yu Sunakawa ◽  
Wataru Ichikawa ◽  
Akihito Tsuji ◽  
Tadamichi Denda ◽  
Yoshihiko Segawa ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Prognostic Impact ◽  
Wild Type ◽  
Phase Ii Trials ◽  
Exon 2 ◽  
Free Survival ◽  
Primary Tumor Location ◽  
Kras Exon

613 Background: Sub-analyses of US and European randomized trials have demonstrated that primary tumor location is a critical prognostic factor in mCRC treated with 1st-line chemotherapy; moreover, left-sided tumor location may be a predictor of cetuximab efficacy in KRAS exon 2 wild-type tumors (Loupakis F, et al. J Natl Cancer Inst 2015; von Einem JC, et al. J Cancer Res Clin Oncol 2014). We therefore investigated the prognostic impact of primary tumor location on outcomes of Japanese pts enrolled in JACCRO CC-05 or CC-06 trial, which evaluated efficacy of cetuximab in combination with FOLFOX or SOX, respectively, for mCRC with KRAS exon 2 wild-type tumors. Methods: This study evaluated the association of tumor location with overall survival (OS) and progression-free survival (PFS) in mCRC pts from 2 phase II trials of 1st-line therapy; JACCRO CC-05 of cetuximab plus FOLFOX (n= 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n= 67, UMIN000007022). Tumors proximal or from left flexure to rectum were defined as right-sided or left-sided, respectively. Results: In total of 124 pts of the 2 trials, 110 pts were assessable for the primary tumor location: 90 pts with left-sided tumors and 20 pts with right-sided tumors. In the population consists of 110 evaluable pts, median PFS was 9.4 months, and median OS was 33.9 months. Left-sided tumors were significantly associated with longer OS (36.2 months vs. 12.6 months, HR 0.28, 95%CI 0.15-0.53, p< 0.0001) and PFS (11.1 months vs. 5.6 months, HR 0.47, 95%CI 0.29-0.82, p= 0.0041) compared to right-sided tumors. The association was evident in the group of FOLFOX (p< 0.0001 for OS and p= 0.0002 for PFS), while there was a trend in OS of the group of SOX (p= 0.079). In the FOLFOX-group, median OS and PFS were 5.7 and 3.0 months, respectively, for right-sided tumors (n= 9) and 42.8 and 11.3 months, respectively, for left-sided tumors (n= 43). Conclusions: Our study demonstrates that primary tumor location may serve as a predictor of prognosis of mCRC pts treated with cetuximab plus oxaliplatin-based therapy, potentially confirming the prognostic impact of tumor location.

Indication and results of surgery following imatinib treatment of locally advanced or metastatic GI stromal tumors (GIST)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9500-9500 ◽  
Author(s):  
P. Hohenberger ◽  
C. Langer ◽  
S. Pistorius ◽  
I. Iesalnieks ◽  
E. Wardelmann ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Multivisceral Resection ◽  
Tumor Location ◽  
Institutional Setting ◽  
R0 Resection ◽  
Imatinib Treatment ◽  
Randomised Trials ◽  
Free Survival

9500 Background: Imatinib mesylate efficiently induces tumor remission in advanced GIST however the curve of progression-free survival (PFS) in the large randomised trials does not reach a plateau. Surgery after achieving a PR is often recommended to remove tumor remnants or seems to be the treatment of choice to control tumor progression not or no longer controlled by drugs. The true impact of surgery is unclear and we analysed the indication and outcome of resective procedures including patients treated outside randomised trials. Patients: In a multi-institutional setting, we collected data from 113 patients after surgery for histologically confirmed GIST after imatinib treatment since April 2002. Primary tumor location: esophagus 3, stomach 23, small bowel 46, rectum 21, extraintestinal 20 pts. Indication for resection: to remove remnants of tumor sites responding well to imatinib 44 pts, resection of progressive lesions 55 pts, resection of a primary tumor after intended neadjuvant treatment 14 pts. Median duration of imatinib treatment prior to surgery was 11 (7–30) months for responding tumors, 14 months (4–28) for progressive lesions and 7 months (3–14) in the neoadjuvant group. Results: Median follow-up postoperatively is 16 months. Operative procedures: hepatic resection 13 pts., abdomino-perineal excision/anterior resection 27 pts, multivisceral resection 73 pts, peritoneal debulking 31 pts. An R0 resection could be achieved in 72% in the PR group, 86% in the neoadjuvant group, but only 26% in the progression group, postop. mortality was 1.7%. Median PFS in the R0 group is 16 (7-39) months and 7 months (2-25±) in the progressive group. In 14 pts imatinib treatment was not continued after R0 resection, 8 pts developed a recurrence. Conclusion: Progression-free survival after R0 resection of responding GIST is encouraging and the data could be used for planning a randomized trial of delayed vs. immediate resection in responding lesions after criteria ‘best response’ are agreed upon. Outside a trial, GIST patients developing a good PR with imatinib should be evaluated for resection as early as possible. However, even patients with a limited number of progressive lesions may benefit from surgery for a longer duration of time. [Table: see text]

Comparison of efficacy and tolerance of first-line palliative chemotherapy EOX and mDCF regimens in patients with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 135-135 ◽  
Author(s):  
Sebastian Ochenduszko ◽  
Kamil Konopka ◽  
Miroslawa Puskulluoglu ◽  
Katarzyna Urbanczyk ◽  
Andrzej Budzynski ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Palliative Chemotherapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Grade 3

135 Background: The aim of the study was to compare efficacy and tolerance of first-line palliative chemotherapy EOX (epirubicin/oxaliplatin/capecitabine) and mDCF (docetaxel/cisplatin/5FU/leucovorin) regimens in patients with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors. Methods: Each chemotherapy regimen was assigned with 21 patients. Planned treatment consisted of 12 every-two-weeks mDCF cycles (docetaxel 40 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1, 5FU 1000 mg/m2/d days 1 and 2, cisplatin 40 mg/m2 day 3) or 8 every-three-weeks EOX cycles (epirubicin 50mg/m2 day 1, oxaliplatin 130mg/m2 day 1, capecitabine 1250mg/m2/d days 1 to 21). The primary endpoint was overall survival in all patients who commenced at least one chemotherapy cycle. Results: Median progression-free survival was 5.8 months in EOX group and 7.5 months in mDCF group (p=0.11), and median overall survival was 8.5 months and 12.0 months respectively (p=0.219). Due to toxicity, patients in the EOX arm had more frequent reductions of cytostatics doses (42.9% vs 5.0%; p=0.009) as well as delays in the administration of subsequent chemotherapy cycles (81.0% vs 65.0%; p=0.424). Rates of all grade 3 or 4 adverse events were comparable between both arms (76.19% in the EOX vs 70.0% in the mDCF; p=1.000). Toxicities that occurred more frequently in the EOX group compared to mDCF group were: nausea (28.6% vs 5.0%; p=0.093), thromboembolic events (19.0% vs 10%; p=0.663) and grade 3 or 4 neutropenia (71.4% vs 55.0%; p=0.443). Conclusions: In this patients population with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors treatment with mDCF regimen was associated with a statistically non-significant 3.5 month longer median overall survival without increase in toxicity. Updated data will be presented.

scholarly journals Nivolumab in Combination With Platinum‐Based Doublet Chemotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer

2016 ◽  
Vol 34 (25) ◽  
pp. 2969-2979 ◽  
Author(s):  
Naiyer A. Rizvi ◽  
Matthew D. Hellmann ◽  
Julie R. Brahmer ◽  
Rosalyn A. Juergens ◽  
Hossein Borghaei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Doublet Chemotherapy

Purpose Nivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non–small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC). Patients and Methods Patients (N = 56) received nivolumab (intravenously) plus PT-DC concurrently every 3 weeks for four cycles followed by nivolumab alone until progression or unacceptable toxicity. Regimens were nivolumab 10 mg/kg plus gemcitabine-cisplatin (squamous) or pemetrexed-cisplatin (nonsquamous) or nivolumab 5 or 10 mg/kg plus paclitaxel-carboplatin (all histologies). The primary objective was to assess safety and tolerability. Secondary objectives included objective response rate and 24-week progression-free survival rate (per Response Evaluation Criteria in Solid Tumors version 1.1); exploratory objectives included overall survival (OS) and response by tumor programmed death ligand-1 expression. Results No dose-limiting toxicities occurred during the first 6 weeks of treatment. Forty-five percent of patients (25 of 56 patients) reported grade 3 or 4 treatment-related adverse events (AEs); 7% of patients (n = 4) had pneumonitis. Twenty-one percent of patients (n = 12) discontinued all study therapy as a result of treatment-related AEs. Objective response rates for nivolumab 10 mg/kg plus gemcitabine-cisplatin, nivolumab 10 mg/kg plus pemetrexed-cisplatin, nivolumab 10 mg/kg plus paclitaxel-carboplatin, and nivolumab 5 mg/kg plus paclitaxel-carboplatin were 33%, 47%, 47%, and 43%, respectively; 24-week progression-free survival rates were 51%, 71%, 38%, and 51%, respectively; 2-year OS rates were 25%, 33%, 27%, and 62%, respectively. Responses were achieved regardless of tumor programmed death ligand-1 expression. Conclusion The safety profile of nivolumab plus PT-DC was consistent with that expected for individual agents; however, treatment discontinuation related to AEs was greater with the combination. Encouraging activity was observed, especially for the nivolumab 5 mg/kg plus paclitaxel-carboplatin group, with a 2-year OS rate of 62%.

Immediate and long-term results of the first line chemotherapy in patients with metastatic triple negative breast cancer. Final analysis of randomized study

2020 ◽  
pp. 75-80
Author(s):  
S.A. Lyalkin ◽  
◽  
L.A. Syvak ◽  
N.O. Verevkina ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Randomized Study ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Group 2 ◽  
Line Chemotherapy ◽  
Group 1

The objective: was to evaluate the efficacy of the first line chemotherapy in patients with metastatic triple negative breast cancer (TNBC). Materials and methods. Open randomized study was performed including 122 patients with metastatic TNBC. The efficacy and safety of the first line chemotherapy of regimens АТ (n=59) – group 1, patients received doxorubicine 60 мг/м2 and paclitaxel 175 мг/м2 and ТР (n=63) – group 2, patients received paclitaxel 175 мг/м2 and carboplatin AUC 5 were evaluated. Results. The median duration of response was 9.5 months (4.5–13.25 months) in patients received AT regimen and 8.5 months (4.7–12.25 months), in TP regimen; no statistically significant differences were observed, р=0.836. The median progression free survival was 7 months (95% CI 5–26 months) in group 1 and 7.5 months (95% CI 6–35 months) in group 2, p=0.85. Both chemotherapy regimens (AT and TP) had mild or moderate toxicity profiles (grade 1 or 2 in most patients). No significant difference in gastrointestinal toxicity was observed. The incidence of grade 3–4 neutropenia was higher in patients of group 2 (TP regimen): 42.8% versus 27% (р<0.05). Conclusions. Both regimens of chemotherapy (AT and TP) are appropriate to use in the first line setting in patients with metastatic TNBC. Key words: metastatic triple negative breast cancer, chemotherapy, progression free survival, chemotherapy toxicity.

An Italian, multicenter, real-world, retrospective study of first-line pazopanib in unselected metastatic renal-cell carcinoma patients: the ‘Pamerit’ study

2020 ◽  
Author(s):  
Alessandra Mosca ◽  
Ugo De Giorgi ◽  
Giuseppe Procopio ◽  
Umberto Basso ◽  
Giacomo Cartenì ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Renal Cell Cancer ◽  
Real World ◽  
Renal Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Metastatic Renal Cell Cancer ◽  
Metastatic Rcc

Abstract Objective Despite the current immunotherapy era, VEGFR inhibitors maintain effectiveness in metastatic renal cell cancer. Real-world data concerning pazopanib are limited. The aim of this study is to add information about efficacy and safety of pazopanib as first-line treatment in metastatic renal cell cancer patients not enrolled into clinical trials. Methods Retrospective analysis (the PAMERIT study) of first-line pazopanib in real-world metastatic renal cell cancer patients among 39 Centers in Italy. Outcomes were progression-free survival, overall survival, objective response rate and treatment-related adverse events. Kaplan–Meier curves, log-rank test and multivariable Cox’s models were used and adjusted for age, histology, previous renal surgery, International Metastatic RCC Database Consortium score and pazopanib initial dose. Results Among 474 patients, 87.3% had clear cell metastatic renal cell cancer histology. Most of them (84.6%) had upfront renal surgery. Median progression-free survival and overall survival were 15.8 and 34.4 months, respectively, significantly correlating with International Metastatic RCC Database Consortium’s good prognosis (P &lt; 0.001), ECOG PS 0 (P &lt; 0.001), age (&lt;75 years, P = 0.005), surgery (P &lt; 0.001) and response to pazopanib (P &lt; 0.001). After 3 months of pazopanib, overall disease control rate have been observed in 76.6% patients. Among International Metastatic RCC Database Consortium’s favorable group patients, 57/121 (47%) showed complete/partial response. No unexpected AEs emerged. Conclusions In this real-world study, metastatic renal cell cancer patients treated with first-line pazopanib reached greater progression-free survival and overall survival than in pivotal studies and had high response rates when belonging to International Metastatic RCC Database Consortium’s favorable group, without new toxicities. Pazopanib has been confirmed a valid first-line option for International Metastatic RCC Database Consortium’s good prognosis metastatic renal cell cancer patients who cannot be submitted to immunotherapy.

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