Sex differences in efficacy and toxicity of first-line treatment of metastatic colorectal cancer (CRC): An analysis of 18,399 patients in the ARCAD database.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4029-4029
Author(s):  
Anna Dorothea Wagner ◽  
Manel Rakez ◽  
Benoist Chibaudel ◽  
Richard Adams ◽  
John Raymond Zalcberg ◽  
...  
Keyword(s):  
Sex Differences ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Tumor Characteristics ◽  
First Line ◽  
Braf Mutations ◽  
Cox Models ◽  
The Impact

4029 Background: The clearance of 5-FU differs significantly between men (M) and women (W). Adjuvant chemotherapy (CT) for CRC has a higher toxicity in W. The impact of sex on efficacy and toxicity in first-line trials of metastatic CRC (mCRC) is unknown. Methods: We analyzed patient (pt) and tumor characteristics, toxicities (nausea (AE1), vomiting (AE2), diarrhea, neutropenia (AE3)) and efficacy (overall survival (OS), progression-free survival (PFS)) according to sex in the following treatment groups: A: CT alone, B: CT + bevacizumab, C: CT + EGFR-antibodies, with subgroup analyses in the CT alone group for single-agent, doublets and triplets, as well as irinotecan- and oxaliplatin-based regimens. Pts from trials with treatments still used today and all relevant data available were eligible. OS and PFS were assessed using Kaplan-Meier and Cox models adjusted for primary tumor location and performance status (PS). Results: We included 28 trials with 18.399 pts (11.352 M and 7.047 W). W were younger (61 vs. 63 years), had more often a PS of 1 (49 vs 45%), BRAF mutations (10 vs. 7%), right-sided tumors (42 vs. 35%) and less often rectal tumors (26 vs. 32%). Significant differences in toxicity are reported in table. Rates of diarrhea were similar. There was no sex disparity in OS in the predefined subgroups except for pts receiving triplets where OS was better in M (HRadj=1.39 (1.05 - 1.85)). Median (interquartile range) OS in months for M and W was 16.7 (9.2-27.4) and 16.2 (8.9-27.2) in group 1, 21.9 (12.7-37.5) and 22.3 (12.9 – 39.0) in group 2, and 26.8 (14.6-45.3) and 24.8 (12.3-49.2) in group 3. HRsadj (W vs M) (95% CI), p values for OS were 1.02 (0.96-1.09), .557, 0.92 (0.83-1.03), .142, 0.99 (0.85-1.14), .866. Conclusions: M and W with mCRC differ significantly regarding patient and tumor characteristics. The significant higher toxicity in W does not translate in a higher treatment efficacy. Apart from known sex differences in pharmacokinetics of 5-FU, differences in pharmacodynamics must be postulated. [Table: see text]

HSR19-085: A Real World Observational Assessment of the Impact of Immunotherapy on the Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)

2019 ◽  
Vol 17 (3.5) ◽  
pp. HSR19-085
Author(s):  
Belqis El Ferjani ◽  
Sheenu Chandwani ◽  
Meita Hirschmann ◽  
Seydeh Dibaj ◽  
Emily Roarty ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Real World ◽  
Performance Status ◽  
Single Agent ◽  
Small Cell ◽  
Cancer Center ◽  
Small Cell Lung ◽  
First Line ◽  
Treatment Choices ◽  
The Impact

Background: NSCLC is the leading cause of cancer-related mortality worldwide. Recently reported clinical trials have firmly established the role of PD-1 and PD-L1 inhibitors in the treatment of patients (pts) with metastatic NSCLC (mNSCLC). We have established the prospective, observational, real-world Advanced Non-Small Cell Lung Holistic Registry (ANCHoR) to understand how the advent of immunotherapy impacts treatment choices and clinical outcomes. Objectives: The aim of this analysis is to measure the impact of immunotherapy on the treatment choice for the first-line treatment of mNSCLC and to determine the link between PD-L1 expression and the treatment choices made in routine clinical practice at the MD Anderson Cancer Center (MDA). Methods: From May 1, 2017, to June 30, 2018, English-speaking pts with mNSCLC at MDA who provided written informed consent were enrolled in ANCHoR and longitudinally followed. The PD-L1 testing rates were captured and the treatment decisions made were also captured and tabulated. The time of data cutoff for this study is June 30, 2018. Results: Of the 296 pts enrolled in the registry at the time of data cutoff, there were 49.7% males, 82.1% white, 45.9% ≥65 years old, 69.3% smokers, 83.1% with an initial stage IV diagnosis, 87.2% with nonsquamous histology, 36.1% with bone metastasis, 29.4% with brain metastasis, 43.2% with 0–1 performance status, and 21.6% with a known EGFR or ALK mutation. A total of 233 pts had been tested for PD-L1 (78.7%). Predominant reasons for not testing (63 pts) include not having available tissue (26 pts) or the test was not requested by the physician (31 pts). As of June 30, 2018, 38.5% of patients received immunotherapy as first-line therapy either as a single agent (18.9%, 56 pts) or in combination with chemotherapy (19.6%, 58 pts). Only 35.8% of the patients received platinum doublet chemotherapy alone. Two pts received chemotherapy combined with an anti-angiogenesis agent (0.68%). Targeted therapy was utilized either as a single agent (20.6%) or in combination with immunotherapy (2.4%). Conclusion: Immunotherapy is now utilized as a single agent or in combination in more than one-third of patients with mNSCLC. These numbers are expected to increase as data from recently reported studies get incorporated into common clinical practice. Compared to historic experience, there has been a dramatic decline in the use of chemotherapy with an anti-angiogenesis agent.

Randomized phase 2 study of maintenance pemetrexed (Pem) versus observation (Obs) for patients (pts) with malignant pleural mesothelioma (MPM) without progression after first-line chemotherapy: Cancer and Leukemia Group B (CALGB) 30901 (Alliance).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8517-8517 ◽  
Author(s):  
Arkadiusz Z. Dudek ◽  
Xiaofei F. Wang ◽  
Lin Gu ◽  
Tom Stinchcombe ◽  
Robert Arthur Kratzke ◽  
...  
Keyword(s):  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase 2 ◽  
First Line ◽  
Efficacy Analysis ◽  
Phase 2 Trial ◽  
Group B ◽  
Line Chemotherapy ◽  
Randomized Phase 2

8517 Background: Standard front-line chemotherapy for advanced MPM is (Pem and a platinum; optimal treatment duration is unknown. We performed a randomized phase 2 trial (NCT01085630) to determine if continuation of single-agent Pem after 4-6 cycles of Pem-platinum would improve progression-free survival (PFS). Methods: Eligible pts had histologically confirmed unresectable MPM, and performance status (PS) 0-1. Pts with at least stable disease following 4-6 cycles of Pem-platinum were stratified by first-line regimen (cis- or carboplatin) and histology (epithelioid versus other) and randomized 1:1 to Obs or continuation of Pem until progression. The primary endpoint was PFS. We assumed that Obs produced a median (m) PFS of 3 months (mo) and Pem would yield a 100% improvement in mPFS to 6 mo; 60 eligible pts (30 per arm) were to be randomized. Results: 72 pts from 30 sites registered 12/10-6/16. The study closed early due to slow accrual once 53 pts were randomized; 49 eligible pts (22 Obs, 27 Pem) are included in the efficacy analysis. Pt characteristics (Obs/Pem): age: median (range) 70 (39-85)/70 (52-87); male 68%/78%; PS 0 27%/33%; epithelioid histology 77%/70%; first-line cisplatin 27%/26%. A median of 4 cycles of Pem (range 1-33) was delivered; 22% of pts required dose modification. mPFS was 3 mo on Obs and 3.4 mo on Pem (hazard ratio (HR) 0.99; 95% CI: 0.51-1.90; p=0.9733). Median overall survival (mOS) was 11.8 mo for Obs, and 16.3 mo for Pem (HR 0.86; 95% CI 0.44-1.71; p=0.6737). Toxicities ≥ grade 3 on Pem included anemia 8%, lymphopenia 8%, neutropenia 4%, and fatigue 4%; there were no grade 5 toxicities. A higher baseline level of serum mesothelin related peptide (SMRP) was associated with worse PFS (HR 1.861, p=0.049). Baseline osteopontin did not significantly affect PFS (p=0.3630). Conclusions: Although it was well tolerated, maintenance Pem following initial Pem/platinum doublet chemotherapy does not improve PFS in MPM patients. High baseline SMRP was associated with shorter PFS. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org . Clinical trial information: NCT01085630.

Prognostic and predictive impact of primary tumor sidedness in first-line trials for advanced colorectal cancer: An analysis of 7,828 patients in the ARCAD database.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 188-188 ◽  
Author(s):  
Jun Yin ◽  
Romain Cohen ◽  
Zhaohui Jin ◽  
Heshan Liu ◽  
Levi Pederson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Primary Tumor ◽  
Performance Status ◽  
Progression Free Survival ◽  
Hepatic Flexure ◽  
First Line ◽  
Cox Models ◽  
Colon Cancers ◽  
Kaplan Meier ◽  
Metastatic Sites

188 Background: Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the prognostic and predictive impact of PTS on outcomes. Methods: PTS data of 7,828 mCRC patients (pts) from 10 first-line randomized trials in the ARCAD database were pooled. PTS was defined as right-sided (RS) or left-sided (LS) if tumor arose from the cecum to the hepatic flexure or from the splenic flexure to the rectum, respectively; transverse colon cancers were not included. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status (PS), prior radiation/chemo, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (anti-EGFR plus chemotherapy vs. chemotherapy alone). Results: Compared to RS pts (2407, 31%), LS pts (5421, 69%) had better OS (median: 21.6 v 16.8 mos; HRadj: 0.73, 95% CI 0.69-0.78, P < .001) and PFS (median 8.4 v 7.2 mos; HRadj: 0.81, 95% CI 0.76-0.86, P < .001). Results were consistent among subgroups defined by age, sex, PS, metastatic sites and chemo backbone (irinotecan- and oxaliplatin-based). Interaction between PTS and KRAS mutation was significant (Pinteraction< .001): LS is associated with better prognosis only among KRAS wild-type (wt) (HRadj: OS 0.62, 95% CI, 0.55-0.70; PFS 0.71, 95% CI 0.63-0.80), but not among KRAS mutated pts. Among KRAS wt pts, survival benefit from anti-EGFR was observed for LS, but not for RS (table). Conclusions: The prognostic value of PTS is restricted to the KRAS wt population. PTS is predictive of anti-EGFR efficacy, with a significant improvement of survival for LS mCRC pts. These results suggest treatment stratification in mCRC studies by both PTS and KRAS status. [Table: see text]

scholarly journals Associations of incidence of common adverse events (AEs) and survival outcomes in metastatic colorectal cancer (mCRC) patients (pts) treated with first line chemotherapy: Findings from 9,812 pts in the ARCAD database.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 617-617
Author(s):  
Danielle Angela Ferraro ◽  
John Raymond Zalcberg ◽  
Qian Shi ◽  
Jeffrey P. Meyers ◽  
Matthew T. Seymour ◽  
...  
Keyword(s):  
Randomized Trials ◽  
Progression Free Survival ◽  
Cytotoxic Agents ◽  
First Line ◽  
Cox Models ◽  
Free Survival ◽  
Conflicting Evidence ◽  
Ecog Ps ◽  
The Impact ◽  
Entire Treatment

617 Background: There is limited, often conflicting evidence about AE timing, severity or associations with outcomes with the use of cytotoxic agents in cancer treatment. We investigated the impact on overall survival (OS) and progression-free survival (PFS) of selected common AEs (neutropenia, diarrhea, nausea, vomiting, neuropathy) occurring in patients receiving first line oxaliplatin (Oxa)- and/or irinotecan(Iri)-based regimens for mCRC. Methods: The CTCAE grading scores of at least one AE of interest were available on 9812 pts treated with chemotherapy alone (median age 63; 62.4% male, 50.1% ECOG PS 0) from 17 1st-line randomized trials. Patients who also received biologics were excluded in the primary analyses. AEs occurring during the first 6 weeks of treatment and entire treatment were analyzed by stratified multivariable Cox models in relationship to OS/PFS. 55.7% pts received Oxa- regimens, 35.7% Iri-regimens, and 8.6% combined Oxa- and Iri-regimens. Results: Within the first 6 weeks of treatment, G3+ neutropenia (HRadj= 1.3, 95% CI, 1.06-1.59, padj 0.01), diarrhea (HRadj= 1.48, 95% CI, 1.23-1.79, padj < .0001), nausea (HRadj= 1.53, 95% CI, 1.17-1.99, padj 0.002) and vomiting (HRadj= 1.56, 95% CI, 1.18-2.07, padj 0.002) were associated with significantly worse OS for Iri-regimens, but only G3+ nausea predicted for worse OS for Oxa- regimens (HRadj= 1.61, 95% CI, 1.18-2.21, padj 0.003). For AEs experienced at any time, G3+ neutropenia and neuropathy were significantly associated with longer PFS and OS for Oxa-regimens, while G3+ vomiting and nausea were associated with worse OS for both Oxa- and Iri-based regimens. Sensitivity analysis showed largely concordant results by including pts who also received biologics. Conclusions: The association between more severe selected AEs and outcome varies between AEs and is influenced by timing of the occurrence. More severe selected AEs occurring early in treatment are associated with worse outcomes. In contrast, for AEs occurring at any time, G3+ neutropenia and neuropathy predicted for longer PFS and/or OS in Oxa-treated pts.

Predictive biomarkers to improve treatment of metastatic colorectal cancer (mCRC): Outcomes with cetuximab plus FOLFIRI in the CRYSTAL trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4068-4068 ◽  
Author(s):  
C. Kohne ◽  
D. Stroiakovski ◽  
C. Chang-chien ◽  
R. Lim ◽  
T. Pintér ◽  
...  
Keyword(s):  
Antibody Therapy ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Braf Mutations ◽  
Mutation Status ◽  
Significance Level ◽  
Line Of Therapy ◽  
The Impact

4068 Background: KRAS oncogene mutation status is predictive of efficacy of cetuximab alone or combined with chemotherapy (CT) in mCRC. Previous data from the phase III CRYSTAL trial showed that adding cetuximab to FOLFIRI in first-line mCRC significantly improved the overall response rate (ORR) and progression-free survival (PFS) in pts with KRAS wild-type (wt) tumors. The serine-threonine kinase BRAF is a direct downstream effector of KRAS. Here, we report the influence of KRAS and BRAF status on mature overall survival (OS) data. Methods: DNA was extracted from archived tumor material where available from randomized pts. KRAS and BRAF mutation status (wt or mutant [mt]) was determined by quantitative PCR. Treatment arms were compared using two-sided log-rank tests (5% significance level) for PFS and OS, and the CMH test for best ORR. Results: The KRAS-evaluable cohort (n=540; 64.4% KRAS wt) was similar to the overall ITT group. In KRAS wt pts, adding cetuximab to FOLFIRI significantly increased the odds for tumor response nearly 2-fold, reduced the risk of progression by 32% and extended median OS from 21.0 months (mo) to 24.9 mo (details in Table ). KRAS mt pts did not benefit from cetuximab. Data on the impact of BRAF mutations on cetuximab activity will be presented at the meeting. In the FOLFIRI and cetuximab + FOLFIRI arms, 31.2% and 36.1% of pts, respectively, received no further line of therapy, while 25.4% and 6.2%, respectively, received EGFR antibody therapy. Conclusions: The benefits of adding cetuximab to CT were greater in KRAS wt pts than ITT pts for all clinically relevant endpoints. KRAS is a key biomarker for selecting a targeted therapy combined with standard CT in first-line mCRC. [Table: see text] [Table: see text]

A prognostic examination of the chemotherapeutic selection for pancreatic cancer patients with peritoneal dissemination: A retrospective study from a single center.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 331-331
Author(s):  
Ryoji Takada ◽  
Tatsuya Ioka ◽  
Hironari Sueyoshi ◽  
Nobuko Ishida ◽  
Takuo Yamai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Retrospective Study ◽  
Survival Rate ◽  
Chemotherapy Regimen ◽  
Peritoneal Dissemination ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Line Chemotherapy

331 Background: Pancreatic cancer(PC) patients(pts) with peritoneal dissemination are poor prognosis. This retrospective study evaluated the prognosis of Gemcitabine(GEM)-based current chemotherapy(G), GEM plus S-1 combination therapy(GS) and single agent of S-1 as 1st line chemotherapy regimen in PC pts with peritoneal dissemination. Methods: This is a retrospective study of PC pts with ascites or peritoneal nodules in the CT or US image who underwent chemotherapy between 2002 and 2011. We collected data on age, sex, Performance Status(PS), tumor location, other metastasis location, status of peritoneal dissemination, CA19-9, CEA, albumin, CRP. We classified 1st line chemotherapy regimen in G, GS and S-1, and we evaluated 1-year survival rate, progression free survival(PFS), overall survival(OS) for the 3 regimens. Results: A total of 81 pts were included. Median age were 64 (38-78), males 50%, PS 0-1 89%. The number of pts treated with G, GS, S-1 was 54, 14, 13. The 1-year survival rate of G, GS and S-1 were 20.3%, 28.5% and 53.8%. The median PFS were 106 days, 84 days and 88 days, respectively. The median OS were 196 days, 154 days, 359 days, respectively. The 1-year survival rate of S-1 was significantly better than that of G (p=0.01). Median PFS and median OS of S-1 didn’t demonstrate the superiority compared with that of G (p=0.40, p=0.08). Conclusions: We suggest the selection of S-1 as 1st line chemotherapy regimen in PC pts with peritoneal dissemination might be effective and we need further investigation.

Impact of first-line bevacizumab therapy on the efficacy of subsequent anti-epidermal growth factor antibodies (anti-EGFR) in metastatic colorectal cancer (mCRC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 685-685
Author(s):  
Matthew E. Burge ◽  
Hui-Li Wong ◽  
Belinda Lee ◽  
Jeanne Tie ◽  
Suzanne Kosminder ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
First Line ◽  
Treatment Benefit ◽  
Exon 2 ◽  
Bevacizumab Treatment ◽  
Epidermal Growth ◽  
Tumour Characteristics

685 Background: The FIRE3 study reported that cetuximab added to first line combination chemotherapy versus the addition of bevacizumab to the same chemotherapy backbone, with a planned switch to the alternative biologic in second line therapy, resulted in improved overall survival. One possible explanation is that the sequence of biologic administration in mCRC impacts on treatment benefit. Examination of the efficacy of anti-EGFR therapy in cohorts where patients have and have not received prior bevacizumab will inform this. Methods: We interrogated our prospective database (ACCORD), which records comprehensive detail on demographics, treatments received and patient outcomes for consecutive mCRC patients in real world practice across multiple institutions in Australia. We included patients receiving 2nd and subsequent line anti-EGFR monotherapy. Disease control rate (DCR) (partial response plus stable disease), progression free survival (PFS) and overall survival (OS) from the start of anti-EGFR were determined as a function of prior bevacizumab use. Results: From a total of 1511 patients treated between 01/10/2002 and 31/12/2014,129 patients treated with single agent anti- EGFR were identified, 75 had received prior bevacizumab. Demographics, performance status and tumour characteristics were similar between the 2 groups. 84% were confirmed KRAS exon 2 wild type. Prior treatment with bevacizumab did not impact DCR (35% vs 40%, p = 0.5065), median PFS (3.0 vs 3.0 months, p = 0.9460) or OS (8.6 vs 8.4 months, HR 0.95, p = 0.8073). Similarly, for bevacizumab treated patients, the time since last dose of bevacizumab to start of anti-EGFR ( < 3 months (n = 26) vs 3-6 months (n = 17) vs > 6 months (n = 32)) did not impact PFS (2.3 vs 3.6 vs 3 months) or OS (8.9 vs 10.1 vs 7.1 months, HR: 0.88, p = 0.82). Conclusions: There was no evident impact of previous bevacizumab treatment, or time from previous bevacizumab treatment, on the efficacy of single agent anti-EGFR therapy in a routine clinical practice cohort. Our data do not support the notion that prior bevacizumab renders tumors more or less sensitive to subsequent anti EGFR therapy.

Impact of overall severity of adverse events (AEs) on long-term outcomes in metastatic colorectal cancer (mCRC) patients (pts) treated with first line systemic chemotherapy: Findings from 3,971 pts in the ARCAD database.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3582-3582
Author(s):  
John Raymond Zalcberg ◽  
Qian Shi ◽  
Danielle Angela Ferraro ◽  
Jeffrey P. Meyers ◽  
Leonard Saltz ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Female Gender ◽  
First Line ◽  
Cox Models ◽  
Hazard Ratios ◽  
Impact On Survival ◽  
Metastatic Sites ◽  
Ecog Ps ◽  
Tumor Types ◽  
The Impact

3582 Background: The prognostic importance of the incidence, severity, type and duration of AEs pts experience during chemotherapy varies between tumor types, and the available evidence across the board is often conflicting. Here we investigated the impact of the overall severity of AEs among pts with mCRC receiving first-line oxaliplatin (Oxa)- and/or irinotecan(Iri)-based regimens. Methods: The overall severity of AE data (i.e., max grade (G) of all AEs) were available on 3,971 pts (median age 61; 60% male, 47% ECOG PS 1+; 57% 2+ metastatic sites) enrolled onto 6 1st-line randomized trials. Around 46%, 45%, and 9% of pts had received Oxa-, Iri-, and Oxa+Iri-based regimens, respectively. Pts receiving biologic agents were excluded. Stratified multivariate Cox models were used to assess the associations with overall survival (OS) and progression-free survival (PFS); adjusted hazard ratios (HRadj) and 95% confidence intervals (CIs) are reported. Results: Pts who only received Oxa-based treatment reported the lowest rate of G3+ AEs (p < .0001) compared to pts treated with Iri- or Oxa+Iri-based regimens. Older age, female gender, and PS 1 or 2+ were associated with higher grade AEs (all p < .0001). Considering AEs experienced within 6w after randomization, 10% and 61% of pts experienced G4+ and G2-3 AEs, respectively. G3+ AEs were associated with a shorter OS for both pts receiving Oxa- (HRadj= 1.2, 95% CI, 1.1-1.3, padj < .0001) and Iri-based regimens (HRadj= 1.4, 95% CI, 1.2-1.5, padj < .0001). For the entire treatment course, 19% and 72% of pts experienced G4+ and G2-3 AEs, respectively. For Oxa-based regimens, pts with G3+ AEs had a longer OS (HRadj= 0.86, 95% CI, 0.78-0.94, padj = .0016), whereas G3+ AEs were associated with a shorter OS (HRadj= 1.2, 95% CI, 1.1-1.4, padj = .0004) for pts treated with Iri-based regimens. Similar patterns were seen for PFS. Conclusions: Pts who reported higher grade AEs during initial treatment (≤6w) have significantly worse outcome than those who do not. Further analyses with treatment exposure/detailed dose-AE profile and its impact on survival are warranted.

scholarly journals A Population-Based Retrospective Study of Biliary Tract Cancers in Alberta, Canada

2021 ◽  
Vol 28 (1) ◽  
pp. 417-427
Author(s):  
Carissa Beaulieu ◽  
Arthur Lui ◽  
Dimas Yusuf ◽  
Zainab Abdelaziz ◽  
Brock Randolph ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Demographic Data ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Intrahepatic Bile Duct ◽  
Population Based ◽  
Phase Iii ◽  
First Line ◽  
Biliary Tract Cancers

Background: Biliary tract cancers (BTC) are uncommon malignancies and are underrepresented in the literature. Methods: We performed a retrospective population-based review of adult patients with biopsy-confirmed BTC in Alberta from 2000 to 2015. Demographic data, risk factors, symptoms, treatment, and staging data were collected and analyzed. Survival analyses were completed. Results: A total of 1604 patients were included in our study, of which 766 (47.8%) were male. The median age at diagnosis was 68 (range 19–99). There were 374 (23.3%) patients with resectable tumors at diagnosis versus 597 (37.2%) with unresectable tumors. Of the patients, 380 (21.5%) received chemotherapy (CT) and 81 (5.0%) underwent radiation therapy. There was a clear trend with worsening stage and performance status associated with shorter median overall survival (OS). Ampulla of Vater tumors had the best median OS (25.69 months), while intrahepatic bile duct cancers had the worst (5.78 months). First-line palliative CT regimens included gemcitabine+cisplatin (OS 14.98 months (mo), n = 212), single agent gemcitabine (OS 12.42 mo, n = 22), capecitabine (OS 8.12 mo, n = 8), and capecitabine+gemcitabine (OS 6.93 mo, n = 13). Patients with advanced or metastatic disease who received first-line gemcitabine+cisplatin had a median OS of 11.8 months (n = 119). Conclusion: BTCs have poor survival. Worse outcomes occur in higher stage and poorer Eastern Cooperative Oncology Group (ECOG) performance status patients across all tumor subtypes. Tumor resectability at diagnosis was associated with better OS. Our study supports the use of gemcitabine+cisplatin as a combination first-line palliative CT, as patients treated in Alberta have a comparable OS to that reported in the ABC-02 phase III study.

Implementation of hepatic artery infusion (HAI) chemotherapy for unresectable colorectal liver metastases (CRLM): The University of Miami experience.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 96-96
Author(s):  
Agustin Pimentel ◽  
Joshua Kronenfeld ◽  
Vikas Dudeja ◽  
Nipun B. Merchant ◽  
Lauren Nicole Gallegos ◽  
...  
Keyword(s):  
Systemic Chemotherapy ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Regional Chemotherapy ◽  
Complete Resection ◽  
Hepatic Artery Infusion ◽  
Braf Mutations ◽  
Perioperative Morbidity ◽  
Academic Center ◽  
Primary Colon

96 Background: In patients with unresectable liver-confined CRLM, regional chemotherapy via HAI in combination with modern systemic chemotherapy (CT) can achieve hepatic disease control and expand surgical resectability. We describe patient selection and early outcomes following implementation of a HAI program at our tertiary referral academic center. Methods: We analyzed demographics, previous systemic treatment, primary tumor location, molecular profiling, extent of hepatic/extrahepatic disease, perioperative HAI outcomes (toxicity, conversion to resection/ablation, radiographic response), and overall survival (OS) in CRLM patients selected for HAI treatment (01/2018—06/2020) after multidisciplinary review. Results: Of 35 patients with unresectable CRLM (primary: colon, n = 24; rectum, n = 11) selected for HAI, 57% were heavily pre-treated (with at least 2 lines of pre-HAI systemic chemotherapy), 71% had a Fong clinical risk score ≥3, 86% presented with synchronous disease, 80% had bilobar metastasis, and 86% had > 5 tumors. All tumors were microsatellite stable, with 20% harboring KRAS/NRAS mutations and none had class I/II BRAF mutations. HAI was initiated at a median 14 (IQR 3, 64) months after CRLM diagnosis, and administered for a median of 7 (range 2, 16) cycles; 91% of patients (31/34) received concurrent HAI and systemic chemotherapy. Although most (69%) patients experienced some degree of hepatic toxicity during HAI therapy resulting in FUDR dose reduction and steroid administration, biliary sclerosis requiring intervention was observed in only 3 (9%) of patients. The overall perioperative morbidity was 17%, and there were no surgical-related 90-day mortalities following HAI pump placement. Excluding patients who initiated HAI treatment within the last 3 months of the study period (n = 3), 13 of 32 patients (41%) were rendered disease-free in the liver following complete resection and/or ablation in combination with HAI/systemic chemotherapy; in the remaining 19 patients (59%), hepatic progression-free survival was 7.3 months (IQR 4, 12). At a median follow-up of 11.2 months, post-HAI median OS for the overall cohort was 12.3 (IQR 7, 20) months. Patients undergoing complete resection/ablation demonstrated improved survival compared with those with progressive disease (median 20 vs 12 months, respectively). Conclusions: Implementation of a HAI program for multimodality liver-directed management of unresectable CRLM is feasible and is associated with meaningful clinical outcomes unlikely to be achieved with systemic therapy alone in heavily pre-treated patients.

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