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Takk. Var litt for kjapp der. Poenget mitt var bare at så lenge presentasjonen i München vil handle om doseeskaleringsstudien, så er det stort sett aktualisering av tidligere verdier vi kan vente oss.
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hello! all absracts related to bile duct in ESMO, including:
*** NUC 1031, Acelarin (from Nucana) 758P
***Amphinex PCI 760P
*** FOLFIRINOX 761P
and many others !
754P - Targeted Therapy based on the Genetic Alterations Prolongs the Progression-free Survival of Patients with Advanced Biliary Tract Cancer
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Feiling Feng (Shanghai, CN)
Background
Targeted therapy based on a certain genetic alteration has been proven to be an effective treatment in some kinds of cancers. We aimed to evaluate the clinical efficacy of personalized targeted therapy for advanced biliary tract cancer (BTC) patients based on individual actionable mutations.
Methods
In this single-center study, the targeted next generation sequencing (NGS) was employed for consecutive 49 patients with BTC and the recommendation of biologic agent was offered according to most potentially targetable genetic alteration of each person. Among 32 patients with stage IV and R2 resection, 21 patients underwent conventional chemotherapy (mGEMOX), while the rest 11 patients received a personalized targeted agent alternative to chemotherapy. The progression-free survival (PFS), overall survival (OS) and disease control rate (DCR) were assessed.
Results
The genomic landscape of 49 patients demonstrated that TP53 (n = 31, 63.3%) variation was most prevalent and was followed by KRAS (n = 12, 24.5%), ARID1A (n = 6, 12.2%), PIK3CA (n = 6, 12.2%), SMAD4 (n = 6, 12.2%), CDKN2A (n = 5, 10.2%) and ERBB4 (n = 5, 10.2%). Further analysis of copy number alterations (CNAs) showed low recurrent amplified genes, such as PIK3CA, SMAD4, FGFR3, SRC, PIK3R2, CDK4, ERBB2, and CDK6. After a median follow-up of 12 months, the targeted group had a significant prolonged PFS (4.5 months vs. 1.5 months, P = 0.014) and a trend of prolonged OS (12.9 months vs. 4.1 months, P = 0.104) in comparison with the chemotherapy group. The DCR in targeted group was a little higher but without significance (63.6% vs. 33.3%, P = 0.142). In addition, the ratio of patients with more than Grade 2 treatment-related toxicities in the targeted therapy group was a little higher compared to that of chemotherapy group but without significance (36.4% vs. 19.0%, P = 0.397).
Conclusions
This mono-center small cohort study suggested that personalized targeted therapy for advanced BTC patients based on individual most potentially actionable mutation detected by NGS, which offered such patients a longer PFS and trends of better OS and DCR, could be an option alternative to conventional chemotherapy.
Editorial Acknowledgement
There is not any editorial assistance for this abstract provided by a third party.
755P - Evaluation of genetic alterations in biliary tract cancer using targeted exome sequencing.
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Heejung Chae (Seoul, KR)
Background
Biliary tract cancer (BTC) is a heterogeneous group of cancers anatomically divided into gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). None of molecular target agents has been proven to improve the prognosis of BTC yet. To gain a deeper understanding of BTC’s pathophysiology and find its new potential therapeutic targets, this study aims to investigate genetic profiles of BTC and their clinical implication.
Methods
A total of 124 patients with adenocarcinoma of biliary tract from Jan 2014 to Feb 2018 were enrolled. With DNA specimen extracted from previously-collected tumor tissue, somatic mutation and copy number analyses were performed using targeted exome sequencing. Data regarding baseline patient characteristics and treatment outcomes were retrospectively obtained from medical records.
Results
Twenty-five patients with GBC (20.2%), 55 with ICC (44.4%) and 44 with ECC (35.5%) were included in the analysis. Genetic mutation were observed in 104 patients (83.8%) and the rest 20 (16.1%) did not have any genetic alterations. The most commonly mutated gene was TP53 (n=55, 44.4%), followed by KRAS (n=36, 29.0%), ARID1A (n=15, 12.1%) and IDH1 (n=12, 9.7%). IDH1/2 mutation appeared more frequently in ICC (n=12, 21.8%, P=0.012) compared to GBC (n=1, 4.0%) or ECC (n=1, 2.3%) while ERBB2 and ERBB3 mutation were found only in GBC and ECC. ERBB2 amplification was observed in 7 patients (4 with GBC and 3 with ICC). Among those, one patient showed 3+ for HER2 test by immunohistochemistry (IHC) while four patients were 2+. Survival outcomes were analyzed among 122 patients who had eventually received palliative chemotherapy for their advanced disease. Patients harboring TP53 mutation had shorter PFS (5.7 vs. 7.1 months, P=0.08) and OS (15.2 vs. 37.8 months, P=0.03) compared to those without TP53 mutation, while IDH1 mutation was likely to be related to favorable PFS (10.6 vs. 6.1 months, P=0.069). On the other hand, there were no significant differences in PFS or OS depending on KRAS or ARID1A mutation.
Conclusions
Genetic profile of BTC is heterogeneous according to its anatomic location. Our results indicate that subgroup of BTC may benefit from targeted therapy such as anti-IDH and anti-HER2 inhibitor.
756P - Interim results of fight-202, a phase 2, open-label, multicenter study of INCB054828 in patients (pts) with previously treated advanced/metastatic or surgically unresectable cholangiocarcinoma (CCA) with/without fibroblast growth factor (FGF)/FGF receptor (FGFR) genetic alterations
Speakers
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Antoine Hollebecque (Villejuif, FR)
Background
Dysregulation of FGFR signaling by FGFR translocations is involved in the pathogenesis of CCA. FGFR2 translocations occur almost exclusively in pts with intrahepatic CCA (iCCA) with an incidence of 13%–15%.1 INCB054828, a selective, potent oral inhibitor of FGFR1, 2, and 3, is being evaluated in a phase 2 study (NCT02924376) of pts with previously treated CCA.
Methods
Pts are enrolled into cohort A (FGFR2 translocations), cohort B (other FGF/FGFR genetic alterations [GA]), or cohort C (no FGF/FGFR GAs) and receive oral INCB054828 13.5 mg once daily on a 21‐day cycle (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary endpoint is objective response rate (ORR) per RECIST v1.1 in cohort A based on independent review. Secondary endpoints include ORR in cohorts B and C, progression-free survival (PFS), overall survival, and safety. We report interim efficacy and safety data.
Results
At data cutoff (27 Nov 2017) 47, 22, and 18 pts were enrolled in cohorts A, B, and C, respectively. In cohort A, 94% (44/47) had iCCA, 98% (46/47) had ECOG PS ≤ 1, and 60% (28/47) received ≥ 2 prior therapies. Of 45 evaluable pts in cohort A, 8 (18%) had a confirmed partial response (PR; 1/8 with unconfirmed complete response) and 26 (58%) had stable disease (3/26 had unconfirmed PRs); the best ORR was 24% (95% CI, 12%–37%). Median PFS was 6.8 months (95% CI, 3.6–9.2 months). No responses were observed in cohorts B or C; median PFS was 1.4 and 1.5 months, respectively. The most common treatment-emergent adverse events (TEAEs) in all pts (N = 87) were hyperphosphatemia (56%), alopecia (36%), and diarrhea (32%). Hyperphosphatemia was managed with diet, phosphate binders, or dose modification. Most frequent grade 3/4 TEAEs were hyponatremia (8%) and hypophosphatemia (7%).
Conclusions
INCB054828 was generally well tolerated and showed preliminary efficacy in pts with previously treated advanced iCCA with FGFR2 translocations. Long-term follow-up data will be presented.
- Graham RP, et al. Hum Pathol. 2014;45:1630-1638.
Clinical trial identification
NCT02924376
757P - M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-β, in Asian patients with pretreated biliary tract cancer: Preliminary results from a phase 1 trial
Speakers
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Changhoon Yoo (Seoul, KR)
Background
Biliary tract cancers (BTCs) are a group of aggressive cancers with limited treatment options. Overall response rates (ORRs) with 2L chemotherapy in BTC are <10%, and no standard of care exists. M7824 is an innovative first-in-class bifunctional fusion protein composed of a human anti–PD-L1 IgG1 monoclonal antibody fused with 2 extracellular domains of the transforming growth factor β (TGF-β) receptor II (a TGF-β “trap”). We report on the safety and efficacy of M7824 in patients (pts) with pretreated BTC.
Methods
In this expansion cohort of the ongoing phase 1, open-label trial NCT02699515, Asian pts who progressed after platinum-based 1L treatment received M7824 1200 mg q2w until confirmed progressive disease, unacceptable toxicity or trial withdrawal. The primary objective is safety/tolerability; secondary objectives include assessment of best overall response per RECIST v1.1. Tumor cell PD-L1 expression was evaluated (antibody clone 73-10).
Results
As of March 20, 2018, 30 pts with pretreated BTC received M7824 for a median duration of 8.9 (range, 2-57.6) wk; 5 pts remained on treatment. The most common treatment-related adverse events (TRAEs) were pyrexia, maculopapular rash (both 13.3%) rash and lipase increase (both 10%); 10 pts (33.3%) experienced grade ≥3 TRAEs. 3 deaths due to AEs were reported; 1 death was due to septic shock (bacteremia, etiology unknown) after 14 doses, and 2 deaths due to interstitial lung disease (ILD), 1 on treatment after 3 doses and 1 with grade 3 ILD after 3 doses that recovered, initiated chemotherapy due to PD, and worsened with death 6 months after initial ILD diagnosis and last M7824 dose. 7 pts had an objective response (ORR, 23.3%, including one late PR pending confirmation), with 4 of 6 PRs ongoing (0.7+, 2.8, 3.9+, 5.5+, 5.6, and 6.9+ mo) and 1 CR ongoing for 5.6+ mo. 1 additional pt had ongoing PR for 7.6+ mo after initial pseudoprogression. Confirmed ORR by PD-L1 expression was 25% and 15.4% in pts with PD-L1+ (≥1%) and PD-L1− tumors, respectively.
Conclusions
M7824 monotherapy has promising efficacy in Asian pts with pretreated BTC, including long-lasting responses in 8 of 30 pts (27%).
Clinical trial identification
NCT02699515
758P - A new ProTide, NUC-1031, combined with cisplatin for the first-line treatment of advanced biliary tract cancer (ABC-08)
Speakers
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Mairead G. McNamara (Manchester, GB)
Background
Cisplatin + gemcitabine (cis/gem) is the global standard of care for 1st-line treatment of patients (pts) with locally advanced/metastatic biliary tract cancer (BTC). No agents have regulatory approval for this disease. Cis/gem achieves an objective response rate (ORR) of 26% and median overall survival (OS) of 11.7 months (ABC-02). Inherent/acquired resistance mechanisms limit gemcitabine efficacy. NUC-1031, a phosphoramidate transformation of gemcitabine, is designed to overcome resistance mechanisms associated with poor gemcitabine response.
Methods
Pts with locally advanced/metastatic BTC, ECOG PS of 0-1 and no prior systemic therapy received NUC-1031 (625 or 725 mg/m2) combined with cisplatin (25 mg/m2) on days 1 + 8 every 21 days. Primary endpoints: safety and determination of RP2D. Secondary endpoints: ORR, pharmacokinetics, progression-free and OS.
Results
14 pts (median age 61 yrs, 8 male; 5 hilar, 4 distal bile duct, 2 intrahepatic, 2 ampullary and 1 gallbladder) were enrolled across cohorts 1 (625 mg/m2, n=8) and 2 (725 mg/m2, n=6). 11 pts completed >1 cycle and were efficacy evaluable, receiving a median of 6.5 cycles (range 3.5-12). ORR was 64% (1 CR, 6 PRs) and DCR: 73%. PFS/OS data collection is ongoing. High, durable intracellular levels of the active anti-cancer metabolite dFdCTP were generated in PBMCs (t1/2=22 h). Treatment was well tolerated with no unexpected AEs/DLTs. Grade 3 TEAEs included neutropenia (14%), fatigue (14%), pyrexia (14%), ALT (7%), AST (7%), GGT (7%) and nausea (7%). Based on high response rate and favourable safety profile, 625 mg/m2 was deemed RP2D. An expansion cohort is ongoing (n=6).
Conclusions
NUC-1031 + cisplatin demonstrated a very high ORR, with a favourable safety profile, and may provide an improved treatment option over cis/gem for advanced BTC. Further development of NUC-1031 in BTC is planned.
Clinical trial identification
NCT02351765
759P - Phase II Study of Evofosfamide (TH-302) monotherapy as a second-line treatment in advanced biliary tract cancer
Speakers
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JEE SUN YOON (Seoul, KR)
Background
Evofosfamide (TH-302), a nitroimidazole-linked prodrug of a brominated version of isophosphoramide mustard, is converted to an activated form and acts as a DNA crosslinking agent when exposed to a hypoxic environment. Biliary tract cancer (BTC) is well known to contain large hypoxic area, and there is no standard 2nd line chemotherapy in advanced BTC. This study is a prospective, open-label, single-arm phase II trial to evaluate the efficacy and safety of evofosfamide as 2nd line treatment in advanced BTC.
Methods
Patients (pts) with unresectable or recurred BTC whose disease progressed after 1st line chemotherapy were enrolled. Pts received evofosfamide at a dose of 340 mg/m2 via intravenous (IV) infusion over 30 minutes on Day 1, 8, and 15 of every 28-day cycle. The primary end point was progression-free survival (PFS) rate at 4-months. Secondary end points included overall survival (OS), PFS, objective response rate (ORR), disease control rate (DCR), metabolic response by 18 F-FDG PET, and safety profile. Response evaluation was done every 8 weeks using RECIST v.1. Metabolic response was evaluated by PERCIST v.1, and toxicity was assessed by CTCAE v4.03.
Results
A total of 20 pts were treated with IP and 16 were response-evaluable.
The median age was 58.7 years (range 54.90 - 62.29). The primary origin of tumor was intrahepatic cholangiocarcinoma in 9 pts, extrahepatic BTC 3, gallbladder cancer 6, and ampulla of vater 2. 16 pts had ECOG PS 0, and 4 had ECOG 1.
There was no objective response, stable disease was observed in 9 pts, results in DCR 56.3%. The PFS rate at 4-months was 31.25%. The median PFS was 3.80 months (95% CI 1.03 - 6.57), and the median OS was 6.37 months (95% CI 3.94 - 8.79). Liver metastasis was associated with poor PFS. Reduction of tumor metabolic activity was observed in 8 pts out of 14 (57.1%).
Majority of adverse events (AEs) were grade 1/2 ; neutropenia(30%), anemia (50%), thrombocytopenia (40%), nausea (15%), arthralgia (5%). Grade 3 anemia was observed in 15%, anorexia 5% and arthralgia 5%. There was no treatment-related death.
Conclusions
Evofosfamide monotherapy showed promising efficacy in terms of disease stabilization and PFS and OS, and acceptable AE profiles used as 2nd line treatment in advanced BTC.
Clinical trial identification
This study is registered with Clinicaltrials.gov, number NCT02433639.
760P - PhotoChemical Internalization of gemcitabine followed by gemcitabine/cisplatin in perihilar cholangiocarcinoma – results from a phase I dose escalation trial
Speakers
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Jörg Trojan (Frankfurt am Main, DE)
Background
Cholangiocarcinoma is a rare cancer with a poor survival and an approximate response rate of 26% and a median PFS/OS of 8.0 and 11.7months respectively with current standard treatment (gemcitabine/cisplatin). Photochemical Internalisation (PCI) is a novel technology that utilizes wave-length specific light (652nm) and a photosensitizer (TPCS2a ; Amphinex®) to enhance the local therapeutic effect of a variety of molecules, including gemcitabine.
Methods
This was a Phase I, dose escalation, multicenter trial of a single PCI induction of gemcitabine (1000 mg/m2) in 16 patients with inoperable perihilar cholangiocarcinoma (CCA). Following the procedure, patients received standard therapy with gem/cis for up to 8 cycles. Patients were on-study for 6 months, and are currently followed for survival. Adverse events, including biliary complications, and tumor effects were characterized.
Results
A total of 16 patients were treated in four different dose cohorts. 11 patients completed the 8 cycles of combination therapy; 5 patients were early withdrawals. PCI of gemcitabine was well tolerated with no Dose Limiting Toxicities, and with a general safety profile characteristic of the patient population included. At 6 months, in the two highest dose cohorts independent reading showed that 7 out of 8 patients had radiologically evaluable tumours. Of these, 2 were complete and 2 partial responses, with one stable disease. In 17/19 target lesions before treatment, a >20% reduction in tumour size was seen, with 12 lesions undetectable at 6 months. Median OS ended at 14.4 months. As of March 2018, 4 of the 16 patients are alive 24.3 to 38.8 months after treatment (overall study average 17.4 months).
Conclusions
In this dose escalation trial of PCI of gemcitabine in perihilar CCA patients, a safe and tolerable dose of light and Amphinex® was established. The overall safety profile and promising results, including a proportion of patients with highly durable objective tumor response, are encouraging. A larger, controlled and randomized study is underway.
Clinical trial identification
NCT01900158
761P - FOLFIRINOX as a first-line chemotherapy for patients (pts) with advanced biliary tract cancer (BTC)
Speakers
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Ayhan Ulusakarya (Villejuif, FR)
Background
FOLFIRINOX is a first-line regimen in the treatment of pancreatic cancer. Historically, BTC and pancreatic cancers were treated similarly with gemcitabine alone or combined with a platinum compound. A growing body of evidence supports the role of fluoropyrimidines in the treatment of BTC.
Methods
We retrospectively analyzed data of all our pts with locally advanced (LA) or metastatic (M) BTC who received FOLFIRINOX as a first-line therapy from 12/2013 to 11/2017 at Paul Brousse university hospital. The main endpoints were OS, TTP, ORR, DC, secondary resection and toxicity.
Results
There were 42 pts: 17 male (40%) and 25 female (60%) pts aged 36 to 84 years (median: 67). Pts had PS of 0 (55%) and 1 (45%). They had intrahepatic cholangiocarcinoma (iCCA) (21 pts, 50%), gallbladder carcinoma (8 pts, 19%), perihilar CCA (7 pts, 17%), distal CCA (4 pts, 10%) and ampulloma (2 pts, 5%). No biopsy could be obtained in 2 pts. BTC was LA or M in 9 (21%) and 33 pts (79%) respectively. Biliary stent was placed in 14 pts (33%). A median (m) of 10 courses was given with m treatment duration of 6 months (mo). At the cutoff on 01/01/2018, regimen was ongoing in 7 pts (18%). Dose intensity (m) was 74, 34 and 1150 mg/m2/w for irinotecan, oxaliplatin and 5FU respectively. The most common nonhematological toxicity was sensory neuropathy: grade 1/2 in 15 pts (36%), no grade 3/4. We observed 15 PR (36%), 16 SD (38%), and 10 PD (24%); 1 pt has not been evaluated for efficacy. Fifteen pts (36%) were alive, 24 pts (57%) died, 3 pts (7%) were lost to follow-up. Four out of 5 pts who underwent resection were alive without disease. At a median follow-up time of 12 mo (1 to 26), mTTP was 9 mo [95%CL, 5 – 12] and mOS was 15 mo [14 – 16]. mTTP was better for LA (not reached) than M-BTC (8 mo), p = 0.05; OS was statistically similar. mTTP was worse in pts with iCCA than other primaries (7 mo [4 – 10] vs 14 mo [9 – 19], p = 0.005); OS was not significantly different. ORR and DC were associated with both better TTP and OS. ORR: mTTP (16 vs 5 mo, p < 0.001), mOS (19 vs 11 mo, p = 0.01); DC: mTTP (10 vs 2 mo, p < 0.001), mOS (18 vs 7 mo, p = 0.002).
Conclusions
First-line FOLFIRINOX offers promising results in patients with LA and M-BTC. It deserves prospective evaluation to further improve outcomes for advanced BTC.
762P - A randomized phase II trial of adjuvant chemotherapy with gemcitabine versus S-1 after major hepatectomy for biliary tract cancer: Kansai Hepato-Biliary Oncology Group (KHBO1208)
Speakers
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Hiroaki Terajima (Osaka, JP)
Background
No adjuvant chemotherapy regimens after major hepatectomy for biliary tract cancer (BTC) have been standardized due to the frequency of adverse events. Survival benefits of adjuvant gemcitabine (GEM) or S-1 (S1) chemotherapy were investigated with the recommended dose determined in our previous clinical trial (KHBO1003), with 10% dose-limited toxicity.
Methods
We performed a phase II multicenter randomized trial. The primary end-point was 1-year recurrence-free survival (RFS), and the secondary end-points were other RFS, overall survival (OS), and others. The following 6-month adjuvant chemotherapy regimens were performed within 12 weeks after R0 or R1 major hepatectomy (hemihepatectomy or trisectionectomy) for BTC: GEM (1000 mg/m2) every 2 weeks or S1 (80 mg/m2/day) for 28 days every 6 weeks. Thirty-five patients were assigned to each arm (alpha error, 10%; beta error, 20%). P values of <0.10 were considered to indicate a statistically significant difference.
Results
No patients were excluded for the per-protocol analysis. There were no statistically significant differences in the patient characteristics of the two arms. The 1-year RFS and the 1-year OS rates of the GEM arm were 51.4% and 80.0%, respectively, while those of the S1 arm were 62.9% and 97.1%, respectively. The 2-year RFS rate, the 1- and 2-year OS rates, and the OS curve of the S1 arm were superior to those of the GEM arm (p=0.0894, p=0.0242, p=0.0679, and p=0.0606, respectively), although the 1-year RFS rate was not significantly different (p=0.334). With regard to the OS curve, the hazard ratio of the S1 group was 0.477 (90% confidence interval, 0.245-0.927).
Conclusions
The adjuvant chemotherapy with S1 may provide better survival benefits compared with that with GEM after major hepatectomy for BTC.
Clinical trial identification
NCT01815307 (March 21, 2013)
763P - Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: A propensity score matched analysis
Speakers
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Siddhartha Yadav (Rochester, US)
Background
The role of neoadjuvant-chemotherapy (NADJ) in cholangiocarcinoma is unknown. The purpose of this study is to evaluate whether NADJ improves overall survival (OS) in cholangiocarcinoma compared to adjuvant-chemotherapy (ADJ).
Methods
Using the National Cancer Database, we identified patients who underwent surgery and chemotherapy for stage I-III cholangiocarcinoma between 2006 and 2014. Patients with metastatic disease at diagnosis or unknown chemotherapy sequence with surgery were excluded. Propensity score for NADJ was calculated by multivariate logistic regression method. Matching with patients who received ADJ was then performed at the ratio of 1:3 using nearest neighbor method with a caliper width of 0.2. Covariates included in matching were: age at diagnosis, sex, race, insurance status, Charlson score, year of diagnosis, location of tumor, tumor grade, clinical stage, and use of radiation.
Results
1450 patients met our inclusion criteria, 299 (20.6%) received NADJ while 1151 (79.3%) received ADJ. The median age at diagnosis was 63 years. Factors associated with higher (p<0.05) use of NADJ compared to ADJ were: ages <54 (35% vs. 23%), white race (91% vs. 86%), year of diagnosis 2012-2014 (48% vs. 40%), intrahepatic tumor location (74% vs. 54%), clinical stage I (46% vs. 38%), and unknown grade of tumor (36% vs. 14%). 279 patients in NADJ group were matched to 698 patients in ADJ group, with resulting standardized mean difference of <0.1 for all covariates. In the matched cohort, patients who received NADJ had a significantly better OS compared to those who received ADJ (HR: 0.79; 95% CI: 0.65 – 0.96, p=0.01). The 1- and 5-year OS was 85.9% and 42.1% respectively for NADJ, while it was 85.0% and 32.7% respectively for ADJ.
Conclusions
In this large national database study, NADJ compared to ADJ improved OS in a select group of patients with cholangiocarcinoma.
767P - Predictive factors of outcome in patients with advanced biliary tract cancer receiving Gemcitabine plus Cisplatin as first-line chemotherapy
Speakers
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Yuko Suzuki (Kashiwa, JP)
Background
Gemcitabine plus cisplatin (GC) is acknowledged as standard chemotherapy for advanced biliary tract cancer (BTC). Few studies have been conducted to identify the prognostic factors in patients receiving this therapy. The purpose of this study was to identify and validate predictive factors of outcome in patients with advanced BTC receiving GC therapy.
Methods
The data of 307 patients with advanced BTC who received GC as the first-line chemotherapy at our institution from January 2007 to June 2017 were reviewed retrospectively. All patients were randomly assigned to the investigation and validation datasets at the ratio of 2:1. Multivariate analysis was conducted to identify the prognostic factors in the investigation dataset (n = 205) and the patients were classified, according to the prognostic factors, into three risk groups, that is, groups with a good, intermediate and poor prognosis. This classification was then applied to the validation dataset (n = 102).
Results
The median overall survival (OS) and 1-year survival rate in the investigation dataset were 13.0 months (95% confidence interval, 11.0-13.9) and 54.7% respectively. Multivariate analysis identified the performance status, pretreatment serum lactate dehydrogenase level and pretreatment neutrophil-to-lymphocyte ratio as independent predictive factors of the OS. The patients were classified into three groups according to the identified prognostic factors, and the outcomes were found to differ significantly among the three groups (p < 0.01). When this classification was applied to the validation dataset, the OS was found to differ significantly among the three risk groups (p < 0.05).
Conclusions
This study identified three predictive factors of outcome, which allowed patients of advanced BTC receiving GC therapy to be classified into three risk groups.
768P - Nomograms predicting survival of patients with advanced or recurrent biliary tract cancer receiving a first-line chemotherapy.
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Naminatsu Takahara (Tokyo, JP)
Background
Some clinical factors are known to be associated with the survival of patients with advanced biliary tract cancer (BTC). A comprehensive model based on these variables is necessary for prediction of an individual’s survival and appropriate patient counseling.
Methods
A nomogram for predicting 1-year survival in patients with advanced BTC in the palliative chemotherapy setting was developed using clinical data from 222 patients with advanced or recurrent BTC who had received first-line systemic chemotherapy from 2006 to 2017 at The University of Tokyo Hospital (Baseline Nomogram). For 214 patients whose initial response to chemotherapy is known, another nomogram (ChemoResponse-based Nomogram) was constructed using the response to chemotherapy as additional variable. Nomogram performance in terms of discrimination and calibration ability was evaluated using the C statistic.
Results
Two different nomograms were developed and subjected to internal validation. The baseline nomogram incorporated 8 baseline clinical variables (age, sex, performance status, tumor location, disease status, CEA, CA19-9, and modified Glasgow prognostic score), whereas the chemoresponse-based nomogram was composed of 9 variables including initial response to chemotherapy evaluated by RECIST ver1.1. Internal validation revealed good performance of the two nomograms in discrimination: C statistics of 0.685 for the baseline and 0.734 for the chemoresponse-based nomogram, which showed better discrimination performance than the baseline nomogram.
Conclusions
This study suggests that individual 1-year survival probability of patients receiving first-line systemic chemotherapy for advanced or recurrent BTC can be reliably predicted by a nomogram-based method incorporating clinical variables and initial response to chemotherapy.
15 Likes
Ble ikke skremt av resultatene til FOLFIRINOX.
Men det ble kanskje Fornybarkrakk? 
1 Like
Er Nucana noen «trussel»?
Mener «Snøffelen» nevnte at det ikke var tilfelle?
1 Like
Nucana kan være en trussel, men foreløpig viser jo de bare til data fra en ‘‘basket trial’’, så det blir jo ikke mulig å gjøre en head-to-head sammenligning her.
Jeg mener Pcib ligger et hestehode foran her med mer data mot en mer spisset pasientgruppe, Extrahepatic cholangiocarcinoma.
2 Likes
Jaxi`s Conclusion - FimaChem (enhancement of chemotherapeutics for localised treatment of cancer) is the winner.
to bad we did not get the numbers from exstensoin study n=7 with the optimal dose and 4 patients who got 2 treatments with Fimaporfin.
My Guess, they are/ will be spectacular.
2 Likes
Mitt inntrykk er at vi leder klart og både i tid og resultater målt mot Nucana og alle andre. Men det er viktig å være først og med best resultater mht til rekrutering tenker jeg.
Derfor håper jeg de får fart i extension studien og får den offenliggjort før pf2 starter. Ellers vil vel mange bli mistroiske til resultatene her.
3 Likes
Vil ikke si jeg ble særlig redd, men det er mest fordi de ikke viser noen resultater fra perihiliar CCA enda. Det kommer kanskje på posteren?
De viser til 7 pasienter med pCCA, og mOS for hele studien med 12mnd follow up var 15mnd og median time to progression var 9mnd. Det er umulig å si noe mer konkret enn det, så da lar jeg heller være. PCIB sine resultater står for seg selv, og de viser mOS 14.4 måneder.
Man må nesten vente til posteren, men de har mange færre pasienter osv.
Dette sier de er en retrospektiv studie på allerede behandlede pasienter, så jeg er heller ikke overbevist om at den studien er den samme som denne hvor de bruker modified FOLFIRINOX og rekrutterer fra 40 sites:
1 Like
Når kommer neste Radforsk podkast? Imorgen?
tror det, blir mye hjertesukk da tenker jeg 
Så de viste 15 mnd mOS med FOLFRINOX, mens PCIB har 14,4mOS for hele sin cohort?
Nå vet vi at resultatene i de to siste dose var mye bedre enn ved de to første, og det vil kanskje gjenskapes når vi får mOS for de to høyeste dosene. Det er små n her da.
Hvis vi ser på hele studien så har jo NUC er bedre ORR på ITT populasjonen (50% vs. 25%) i forhold til PCIB , men det blir en del farget av at de to laveste dosene viste veldig lite effekt.
Sammenlikner vi efficacy evaluable så blir det mer tett (65% ORR for nuc vs. 50% ORR for PCIB) hvor NUC ser bedre ORR, men PCIB har flere CR.
Ta forbehold på at dette er forskjellige pasientpopulasjoner (5 hilar, 4 distal bile duct, 2 intrahepatic, 2 ampullary and 1 gallbladder vs. PCIB sin eCCA).
Mitt inntrykk: Nucana kan se farlig ut, men siden vi ikke har noe resultater på hvordan PCIB og Nucana gjør det head-to-head innad for eCCA så blir det vanskelig å si noe konkret. Hvis mOS for FOLFRINOX er rundt 15 mnd så blir det viktig å vise bra OS data fra de to høyeste dosekohortene. Jeg syns også dette gjorde det litt mer viktig at extensionresultatene hever resultatene for PCIB.
Det er også viktig å huske på at PCIB behandler pasienter med inoperabel CCA, og jeg syns ikke det kommer frem at det er tilfelle for de andre(?), noe som kan ha en del å si for OS til pasientene.
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Ja podkasten kommer imorgen. Jonas vil bla. kommentere mine kritiske innvendinger relatert til fortrinnsemisjonen i PCIB, samt Raforsks engasjement i denne.
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Svar fra RADFORSK :
Hei. Vi spiller inn en Nobelpris-spesial i morgen ettermiddag og en ordinær selskaps/spørsmåls podkast på torsdag formiddag - så regner med at begge er ute før helgen…
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Ja, det blir litt for lite pasienter/informasjon til å gjøre noen særlig god sammenlikning, men vi ser jo at både NUC og FOLFIRINOX har effekt i pasientgruppen. Og så mener jeg det er et annet studie med modified FOLFIRINOX som er verdt å følge med på siden det er ett fase II/III-studie. Det er det jeg har blitt hudflettet for å ha nevnt før.
Anyways, budskapet er å følge med og å ikke tro at noe er en open and shut case. Jeg har også stor tro på dobbel behandling med Amphinex, men det virker å være en stund til de resultatene foreligger siden de skal starte pivotalstudien samtidig som extensionstudiet gjøres ferdig. Det vil si at det kommer til å drøye et godt stykke inn i 2019 (?)
Når PCIB sammenlignes med konkurrenter, er det vel lurt å huske på at det ikke bare handler om å være først og ha det beste alternativet, men også om hvordan du er posisjonert.
Markedsmakt (direkte eller indirekte gjennom partnere), finansiell styrke, lokalisering, relasjoner til portvakter, godkjenningsinstanser, og interesseforeninger, m.m. er alle faktorer som kan spille inn i forhold til hvilket behandlingsalternativ som “vinner”.
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Tja. Onkologimedisin er legene/teamene er oppdatert og det beste vil brukes. Det er stor prestisje og resultatene for pasientene er enorme om de ikke bruker det beste.
Så innen kreft og til dels hjertesykdommer slipper de mye av BP-problemer som andre medisiner sliter med.
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@idioten
Den er jeg med på. Allikevel tror jeg at også enkelte instanser utenfor legene/teamene har påvirkning, og at et selskap med stor markedsmakt også har stor påvirkningskraft ovenfor disse legene/teamene. Har du sterk innflytelse, og det dreier seg om store penger, kan du også overbevise de som må overbevises, og som en av lederne i et visst britisk selskap som hjelper politikere med å vinne valg sa: det behøver ikke være sant så lenge du får folk til å tro på det. (Trist at der er sånn, men sånn er det.)
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Det finnes nok en del smøring av Key Opinion Leaders og utøvelse av markedsmakt. Men for Pcibs del ser jeg ikke helt hvor den skal komme fra, så lenge gem/cis er dagens alternativ. Det kan jo forandre seg, men pdd virker markedet åpent.
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