ESMO Supporter 2018

Displaying One Session

Hall B3 - Room 21 Poster Discussion session
Date
19.10.2018
Time
15:45 - 17:25
Location
Hall B3 - Room 21
Chairs
  • Florian Lordick (Leipzig, DE)
  • Marcel Verheij (Nijmegen, NL)
  • Ann-Lii Cheng (Taipei, TW)
  • Ian Chau (Sutton, GB)
  • Eileen M. O'Reilly (New York, US)
Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

616PD - Quality-of-life (QoL) results from RAINFALL: A randomized, double-blind, placebo (PL)-controlled phase 3 study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy for metastatic gastric or gastroesophageal junction (G-GEJ) cancer

Presentation Number
616PD
Lecture Time
15:45 - 15:45
Speakers
  • Ian Chau (Sutton, GB)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

RAINFALL met its primary endpoint of improved progression-free survival (HR = 0.75, 95% CI 0.61–0.94, median 5.7 vs 5.4 months), but overall survival was not improved (HR = 0.96). No new safety signals were identified compared with other RAM studies. Here we present the QoL results.

Methods

Patients (pts) with untreated metastatic HER2- G-GEJ cancer were randomized to receive RAM (8 mg/kg D1, D8) or PL every 21 days. All pts received Cape (or 5FU) + Cis. Pts completed the EORTC QLQ-C30 (v3) at baseline (BL), before each cycle, and at 30-day follow-up. QoL scores were standardized to a 0-to-100 scale; ≥10-point change was considered clinically meaningful. Two pre-specified analyses were conducted using the ITT population: (1) time to sustained deterioration (TtSD) was from randomization to first worsened score with no subsequent improved or stable score and compared with an unstratified log-rank test; and (2) post-BL QoL assessments were classified as improved, stable, worsened, or not evaluable; rates of improved+stable were compared with Fisher’s exact test.

Rates of improved and stable QoL scores for scales with greatest baseline impairment at select cycles

RAM+Cape/Cis (N = 326), %
PL+Cape/Cis (N = 319), %
Cycle 2 Improved /StableTotalCycle 4 Improved /StableTotalCycle 2 Improved /StableTotalCycle 4 Improved /StableTotal
Global QoL21.2 / 31.352.516.6 / 21.237.721.9 / 31.353.314.1 / 22.937.0
Emotional functioning21.8 / 35.957.719.0 / 28.247.225.4 / 35.460.819.7 / 24.544.2
Fatigue20.9 / 17.538.317.2 / 9.827.019.7 / 23.843.611.9 / 17.629.5
Pain27.6 / 27.655.219.3 / 23.943.327.3 / 26.053.319.4 / 20.139.5
Insomnia20.6 / 37.758.317.2 / 26.443.617.9 / 36.754.515.4 / 23.238.6
Appetite loss21.2 / 33.454.616.6 / 24.841.420.7 / 33.253.916.0 / 21.337.3

Results

Of 645 pts randomized, 312/326 (96%) of RAM+Cape/Cis and 309/319 (97%) of PL+Cape/Cis pts had BL QoL data. Compliance was ≥87% with post-BL assessments while on therapy. BL scores were similar between arms. Based on BL mean scores, highest levels of impairment were seen for global QoL, emotional functioning, fatigue, pain, insomnia, and appetite loss. For all 15 QoL scales, TtSD HRs ranged from 0.80 to 1.13 and all 95% CIs included 1. For all scales and post-BL assessments, rates of improved+stable scores were similar between arms.

Conclusions

For pts with previously untreated, metastatic G-GEJ cancer, QoL was maintained with the addition of RAM to Cape/Cis. Regardless of arm, treatment improved or stabilized most disease-related symptoms.

Clinical trial identification

NCT02314117.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Editorial Acknowledgement

Eli Lilly and Company contracted with Syneos Health for writing support provided by Andrea Humphries, PhD and editorial support provided by Angela C. Lorio, ELS.

Disclosure

I. Chau: Advisory board: Sanofi Oncology, Eli-Lilly, Bristol-Myers Squibb, MSD, Bayer, Roche, Merck Serono, Five Prime Therapeutics; Research funding: Eli-Lilly, Janssen-Cilag, Sanofi Oncology, Merck-Serono, Novartis; Honorarium: Taiho, Pfizer, Amgen, Eli-Lilly. S-E. Al-Batran: Advisory role: Merck, Roche, Celgene, Lilly, Nordic Pharma, Bristol-Myers Squibb, MSD Sharp & Dohme; Speaker: Roche, Celgene, Lilly, Nordic Pharma, AIO gGmbH, MCI, promedicis, Forum für Medizinische Fortbildung; CEO/founder of IKF Klinische Krebsforschung GmbH; Research grants: Sanofi, Merck, Roche, Celgene, Vifor, Medac, Hospira, Lilly, German Cancer Aid (Krebshilfe), German Research Foundation and the Federal Ministry of Education and Research. G. Bodoky: Consulting or advisory role: Bayer, Ipsen, Janssen, Lilly, Novartis, Pfizer, Roche; Travel, Accommodations, Expenses: Janssen, Lilly, Novartis, Pfizer, Roche. G. Folprecht: Honoraria: Merck KGaA; Consulting or advisory role: Baxalta, Bristol-Myers Squibb, Lilly/ImClone, Merck KGaA, Roche/Genentech; Research funding: Merck KGaA. K. Peltola: Personal fees: Orion Pharma, BMS, Pfizer, Roche, MSD, Ipsen, outside the submitted work; Advisory fees and Stock holder: Faron Pharmaceuticals. C. Denlinger: Honoraria: Eli Lilly and Co; Research support (institutional): Eli Lilly and Co, MedImmune, AstraZeneca, Merrimack, Bristol-Myers Squibb, Genentech. A. Liepa, M. Das, R. Wei: Employee, Stockholder: Eli Lilly and Company. C.S. Fuchs: Consultant fees: Lilly, Entrinsic Health, Genentech, Merck, Sanofi, Five Prime Therapeutics, Merrimack, Bayer, Agios, Taiho, Kew, Bain Capital, Unum; Board member: CytomX. All other authors have declared no conflicts of interest.

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

617PD - A phase 3 study of nivolumab (Nivo) in previously treated advanced gastric or gastric esophageal junction (G/GEJ) cancer (ATTRACTION-2): Two-years update data.

Presentation Number
617PD
Lecture Time
15:45 - 15:45
Speakers
  • Taroh Satoh (Suita, JP)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

Nivo monotherapy has shown superior efficacy with manageable safety for G/GEJ cancer refractory to, or intolerant of standard chemotherapy in a phase 3 study (ATTRACTION-2). Here, we report 2-year updated results of survival.

Methods

A total of 493 patients with unresectable advanced or recurrent G/GEJ cancer after failure of two or more previous chemotherapy regimens were randomized in a 2:1 ratio to receive 3 mg/kg Nivo (N = 330) or placebo (N = 163) until progressive disease or unacceptable toxicity. The primary endpoint was overall survival (OS). Updated results of the efficacy and safety were based on ≥ 2-year follow-up after last patient enrollment. As a subgroup analysis, the OS data by BOR was evaluated.

Results

As of data cut-off on February 2018, 2 years after last patient enrollment, the median OS (mOS) was 5.3 months with Nivo versus 4.1 months with placebo (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.51-0.76). The OS rates of Nivo and Placebo were 27.3% and 11.6% at 12 months, and 10.6% and 3.2% at 24 months, respectively. In a OS subgroup analysis stratified by BOR, mOS in PR patients in Nivo arm was not reached. Median OS in SD patients were 9.4 and 7.6 months (HR 0.70, 95%CI 0.44-1.09), and mOS in PD patients were 3.8 and 3.8 months (HR 0.86, 5%CI 0.64-1.16) in Nivo and placebo arm, respectively. In addition, 12-month OS rate in PR patients was 86.7% in Nivo arm. OS rate at 12 months in SD patients were 36.9 and 24.2%, and OS rate at 12 months in PD patients were 12.4 and 6.9% in Nivo and placebo arm, respectively. The safety analysis for 2-year follow-up will be presented.

Conclusions

Nivo has significantly improved OS with 2-year follow-up. In PR and SD patients, the subgroup analysis of OS favored Nivo over placebo.

Clinical trial identification

NCT02267343. Other Study ID Numbers: ONO-4538-12.

Legal entity responsible for the study

Ono Pharmaceutical Co., Ltd.

Funding

Ono Pharmaceutical Co., Ltd and Bristol-Myers Squibb.

Editorial Acknowledgement

We thank Naokazu Gion for providing statistical support, the project leader Mitsunobu Tanimoto (ONO Pharmaceutical,.CO.LTD.).

Disclosure

T. Satoh: Consulting fees: Chugai, Ono, Taiho, Eli Lilly, Daiichi Sankyo; Honoraria: Chugai, Ono, Yakult Honsha, Bristol-Myers Squibb, Merck Serono, Taiho, Eli Lilly, Daiichi Sankyo; Departmental research grants: Chugai, Ono, Yakult Honsha. L-T. Chen: Advisory board role: Ono, BMS, MSD, Eli Lilly, PhamaEngine, Five Prime, Novartis, AstraZeneca; Honoraria: Ono, BMS, MSD, Eli Lilly, PhamaEngine, TTY, SyncoreBio, Five Prime, Novartis, AstraZeneca, Ipsen; Research funds: Novartis, Pfizer, Merck Serono, Polaris, TTY, SyncoreBio, Celgene. Y-K. Kang: Personal fees: Ono Pharmaceutical. Co., Ltd., Bristol-Myers Squibb, Lilly / ImClone, Taiho Pharmaceutical, Novartis, Roche / Genentech, Bayer; Grants: Roche / Genentech, Novartis, Bayer. K. Kato: Research funds: Ono Pharmaceutics, Merck and Co. Shionogi, Merck Serono. H.C. Chung: Consultation honoraria: Taiho, Celltrion, MSD, Lilly, Quintiles, BMS, Merck-Serono; Research funds: Lilly, GSK, MSD, Merck-Serono, BMS-Ono, Taiho; Speaker's bureau: Merck-Serono, Lilly, Foundation-Medicine. J-S. Chen: Research funds: Ono/BMS, MSD, Ill Lilly, Roche; Speaker's bureau: Ono/BMS, MSD, Ill Lilly, TTY Biopharm, Novartis. K. Muro: Honoraria: Ono, Chugai, Bayer, Takeda, Taiho and Eli Lilly; Research funds: MSD, Ono, Daiichi Sankyo, Shionogi, Kyowa Hakko Kirin, Gilead Science. T. Yoshikawa: Honoraria: Ono, Bristol, Lilly, Chugai, Taiho, Yakult, MSD, Abbott, Takeda, Daiichi-Sankyo, Nihon-Kayaku, Kaken-Seiyaku, Olympus, Johnson and Johnson, and Covidien; Research funds: Chugai, Taiho, Yakult, Novartis. T. Tamura: Research funds: Ono, Bristol-Myers Squibb. K-W. Lee: Research funds: Ono Pharmaceutical (to institution). N. Boku: Honoraria: Ono, Bristol-Myers Squibb; Research funds: Ono, Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

619PD_PR - Influence of sex on chemotherapy efficacy and toxicity in oesophagogastric (OG) cancer: a pooled analysis of 4 randomised trials

Presentation Number
619PD_PR
Lecture Time
15:45 - 15:45
Speakers
  • Michael Davidson (London, GB)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

Sex is a contributing factor to inter-patient variability of chemo metabolism and dose-response, potentially influencing both efficacy and toxicity. Use of a triplet chemo regimen comprising an anthracycline, platinum and fluoropyrimidine remains a standard option in first line treatment of advanced OG cancer. Comparative data on the effect of sex on chemo-related toxicity in this tumour type are lacking.

Methods

Data for pts randomised to ECF, ECX, EOF or EOX chemo within 4 UK-NCRI multicentre RCTs of first line treatment in advanced OG cancer were pooled. Demographic and outcome data, and prevalence of all grade and grade ≥3 toxicity were compared between males and females. Adverse events and response rates were compared by Chi-squared test; survival outcomes by log-rank test.

Results

1654 pts were included; 1328 males (80.3%) and 326 females (19.7%). Age and PS were equally distributed; gastric tumours were more prevalent in females (57.4 vs 34.1%). For toxicities captured commonly across all 4 trials there was no significant difference in all grade or grade ≥3 toxicity between females and males (67.2 vs 62.8%; p=0.19). Females experienced significantly higher rates of nausea and vomiting, both all grade (89.3 vs 78.3%; p<0.001) and grade ≥3 (16.7 vs 9.5%; p<0.001); all grade diarrhoea (53.8 vs 46.9%; p=0.027); all grade stomatitis (49.5 vs 40.7%; p=0.004) and all grade alopecia (81.4 vs 74.3%; p=0.009). There was a trend towards increased rates of grade ≥3 neutropaenia and febrile neutropaenia (45.1 vs 40.4% and 11.8 vs 7.7% respectively), although significance was not reached. Males experienced significantly more all grade peripheral neuropathy (49.3 vs 42.6%; p=0.03). There was no difference in PFS or OS by sex; ORR was higher in males (46.6 vs 40.4%), which approached significance (p=0.051).

Conclusions

This represents the largest pooled analysis of sex effect on outcome and toxicity in advanced OG cancer pts treated with equivalent first line chemo. Females demonstrated significantly higher rates of a number of toxicities, primarily GI in nature, and a trend towards increased rates of neutropaenia. Such results suggest that further research on the impact of sex on the efficacy and toxicity of chemo is necessary.

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

Invited Discussant 616PD, 617PD and 619PD_PR

Lecture Time
15:45 - 15:55
Speakers
  • Florian Lordick (Leipzig, DE)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25
Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

Q&A led by Discussant

Lecture Time
15:55 - 16:05
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25
Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

618PD - Progression-free survival and recurrence results for AGITG DOCTOR. Pre-op cisplatin, 5FU & DOCetaxel +/-radioTherapy after poOR early response to cisplatin & 5FU for resectable oesophageal adenocarcinoma.

Presentation Number
618PD
Lecture Time
16:05 - 16:05
Speakers
  • Andrew P. Barbour (Woolloongabba, AU)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

Resectable oesophageal and gastro-oesophageal junction adenocarcinoma patients (pts) without early metabolic response (EMR) to chemotherapy as defined by 18-FDG-PET (PET) show poor survival and major histological response rates (RR) <5%. This multicentre trial previously reported changing neoadjuvant therapy improved major histological RR for early metabolic non-responders (MNR). Grade 3/4 toxicities were seen in 27% of pts on 5-FU + cisplatin (CF); 42% on docetaxel + CF (DCF) and 71% on DCF + concurrent 45Gy radiotherapy (DCFRT). Updated results now report progression-free survival (PFS) and local recurrence.

Methods

Pts had a day 15 PET scan after induction CF. Early metabolic responders (SUVmax decreasing by ≥ 35% from baseline to day 15 PET) received a 2nd CF cycle then oesophagectomy. Early metabolic non-responders were centrally randomised 1:1 to 2 cycles of DCF or DCFRT then oesophagectomy. Primary endpoint was major histological RR (<10% residual tumour). Seconday endpoints were PFS and local recurrence.

Results

From 2009 -2016, 124 pts were recruited. 45 were deemed early metabolic responders. 77 were deemed early metabolic non-responders and 31 allocated DCF and 35 to DCFRT. 11 were not randomised (progression, toxicity, refusal). 2 were not evaluable. Major histological response rates: 7% EMR (CF); 20% DCF; 63% DCFRT. Local recurrence: 5/45 (11%) EMR (CF); 10/31 (32%) MNR allocated DCF; 4/35 (11%) MNR allocated DCFRT. PFS at 36m: 46% (95% CI 31-60%) for EMR; 31% (95% CI 16-48%) for MNR allocated DCF; 46% (95% CI 29- 61%) MNR allocated to DCFRT.

Conclusions

Early metabolic response to CF alone is associated with favourable PFS and low local recurrence rate despite a low major histological RR. The addition of docetaxel in MNR group may augment histological RR but PFS & local recurrence outcomes remained inferior. Further addition of RT to DCF produced the highest histological RR and PFS/local recurrence outcomes matching EMR group. Early PET can enable tailoring of therapy to ‘close the gap’ in outcomes between early metabolic response and early metabolic non-response patients.

Clinical trial identification

Australian New Zealand Clinical Trials Registry: 12609000665235.

Legal entity responsible for the study

The Australasian Gastro-Intestinal Trials Group (AGITG).

Funding

The National Health and Medical Research Council, Australia.

Editorial Acknowledgement

No editorial assistance was accessed for this abstract.

Disclosure

All authors have declared no conflicts of interest.

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

620PD - Influence of enteral nutrition on nutritional status, treatment toxicities, and short-term outcomes in esophageal carcinoma patients treated with concurrent chemoradiotherapy: a prospective, multicenter, randomized controlled study

Presentation Number
620PD
Lecture Time
16:05 - 16:05
Speakers
  • Tao Li (Chengdu, CN)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

To investigate the influence of enteral nutrition on body weight, nutritional status, treatment toxicities, and short-term outcomes in esophageal carcinoma patients with concurrent chemoradiotherapy (CCRT).

Methods

Eigible patients were randomly assigned (2:1 ratio) to EN group or control group. The primary endpoint was the change in body weight from baseline after treatment. The secondary endpoints were nutrition related blood parameter changes, treatment toxicities and outcomes.

Results

Between Mar. 2015 and Jun. 2017, 222 patients from ten hospitals were randomised into the EN group (n = 148) and the control group (n = 74). Patients in EN group lost less body weight compared with the control group (P<.0.05). Participants who received EN had less decline than controls in serum albumin and hemoglobin (P < 0.05). There was no difference in total lymphocyte counts in the two groups. Grade 3/4 leukopenia and infection rates were significantly more frequent in the control group than in the EN group (P < 0.05). Radiation pneumonitis and esophagitis tended to be less frequent in the EN group, albeit insignificantly. Patients supported on EN experienced greater chemoradiotherapy completion rates. There was no significant difference in tumor response between two groups (P > 0.05).

Conclusions

Enteral nutrition can reduce the weight loss of esophageal cancer patients during chemoradiotherapy, improve nutritional status, treatment tolerance, reduce toxicity.

Clinical trial identification

NCT 02399306.

Legal entity responsible for the study

Tao Li.

Funding

Has not received any funding.

Editorial Acknowledgement

none

Disclosure

All authors have declared no conflicts of interest.

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

Invited Discussant 618PD abd 620PD

Lecture Time
16:05 - 16:15
Speakers
  • Marcel Verheij (Nijmegen, NL)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25
Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

Q&A led by Discussant

Lecture Time
16:15 - 16:25
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25
Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

621PD - Phase 2 trial of tepotinib vs sorafenib in Asian patients (pts) with advanced hepatocellular carcinoma (HCC)

Presentation Number
621PD
Lecture Time
16:25 - 16:25
Speakers
  • Baek-Yeol Ryoo (Seoul, KR)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

MET is a potential therapeutic target in HCC. Tepotinib, a potent and highly selective MET inhibitor, has antitumor activity in pts with MET+ tumors. Phase 1b of the current trial (NCT01988493), confirmed the recommended phase 2 dose (RP2D) of tepotinib in Asian advanced HCC pts; here we describe phase 2 outcomes for tepotinib vs sorafenib.

Methods

Asian adults with MET + (2+ or 3+ by immunohistochemistry) advanced HCC (Barcelona clinic liver cancer Stage B/C; Child-Pugh Class A without encephalopathy; Eastern Cooperative Oncology Group performance status 0–1; no prior systemic advanced HCC therapy) were randomized (1:1) to tepotinib 500 mg once daily (RP2D) or sorafenib 400 mg twice daily in 21-day cycles. Endpoints: time to progression (TTP: primary endpoint), safety, progression-free survival (PFS), overall survival (OS) and tumor response. Efficacy was assessed by independent review committee (IRC) and investigators.

Results

Of 90 pts randomized, 75 were included in the efficacy analysis (tepotinib n = 38, sorafenib n = 37): median age 57 [range 31–78] years; 84.0% <65 years old; 94.7% male). TTP by IRC was statistically significantly longer for tepotinib vs sorafenib (2.8 vs 1.4 months; hazard ratio [HR] (90% confidence interval [CI]): 0.42 (0.26, 0.70); p = 0.0043). Median PFS by IRC was also statistically significantly longer for tepotinib (2.8 vs 1.4 months; HR (90% CI): 0.53 (0.33, 0.84); p = 0.0229). Median OS was similar between arms (tepotinib 9.3 vs sorafenib 8.6 months; HR [90%CI] 0.73 [0.43, 1.12]; p = 0.3039). Objective response rate by IRC was 10.5% (tepotinib) vs 0% (sorafenib) (p = 0.0438). There were 4 partial responses, all in the tepotinib arm. IRC outcomes were supported by investigator read data. In the safety analysis, treatment-related treatment-emergent adverse events (TRTEAEs) occurred in 37/45 (82%) and 43/44 (98%) pts and TRTEAEs grade ≥3 in 13/45 (29%) and 20/44 (46%) pts in the tepotinib and sorafenib arms, respectively. No new safety signals were noted.

Conclusions

Tepotinib provided significantly longer TTP and PFS than sorafenib in Asian pts with MET+ advanced HCC, with fewer reported overall and grade ≥3 TRTEAEs.

Clinical trial identification

NCT01988493.

Legal entity responsible for the study

Merck KGaA, Darmstadt, Germany.

Funding

Merck KGaA, Darmstadt, Germany.

Editorial Acknowledgement

Medical writing assistance was provided by Helen Swainston PhD of Bioscript Science (Macclesfield, UK) and funded by Merck KGaA, Darmstadt, Germany.

Disclosure

J-W. Park: Honoraria: Bayer, BMS, Ono; Consulting and Advisory: BMS, Ono, Bayer, Eisai, Midatech, Roche; Corporate-sponsored research: BMS, Ono, Eisai, Bayer, Roche, Blueprint, AstraZeneca, Exelixis. D. Zhou: Employee: Merck Serono. J. Straub: Employee: Merck KGaA. C. Zhao: Employee: EMD Serono. All other authors have declared no conflicts of interest.

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

622PD - Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP) following first-line sorafenib: patient reported outcome results across two phase 3 studies (REACH-2 and REACH)

Presentation Number
622PD
Lecture Time
16:25 - 16:25
Speakers
  • Andrew X. Zhu (Boston, US)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

Ramucirumab (RAM) was studied in patients with advanced HCC and AFP≥400 ng/mL following sorafenib in two global, randomized, double-blind, placebo (PL)-controlled phase 3 studies. REACH-2 met its primary endpoint demonstrating an improved overall survival (OS) for RAM treatment compared to PL, consistent with the benefit observed in pre-specified patients with AFP ≥400 ng/mL in REACH. Patient reported outcome (PRO) analyses of disease-related symptoms in patients from REACH-2, and pooled with patients from REACH with baseline AFP ≥400 ng/mL were performed.

Methods

Eligible patients had advanced HCC, Child-Pugh A, ECOG PS 0 or 1, AFP ≥400 ng/mL, and prior sorafenib. Patients received RAM 8 mg/kg or PL Q2W. PROs were assessed by Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index (FHSI)-8 at baseline, Q6W and end of treatment. Deterioration in FHSI-8 was defined as ≥ 3-point decrease in total score, or a decrease in one categorical response for an individual item. Time to deterioration (TTD) was time from the date of randomization to the first date of deterioration.

Time to deterioration of FHSI-8

Analysis populationREACH-2 N = 292 (RAM 197, PL 95)REACH AFP ≥400 ng/mL N = 250 (RAM 119, PL 131)Pooled REACH-2, REACH AFP ≥400 ng/mL N = 542 (RAM 316, PL 226)
Total score, median3.7 mo RAM vs 2.8 mo PL2.9 mo RAM vs 1.6 mo PL3.3 mo RAM vs 1.9 mo PL
HR (95% CI)
Total score0.799 (0.545, 1.171)0.690 (0.470, 1.014)0.725 (0.559, 0.941)
Lack of energy1.098 (0.741, 1.627)0.884 (0.605, 1.292)0.942 (0.724, 1.225)
Nausea0.809 (0.498, 1.315)0.931 (0.586, 1.479)0.821 (0.589, 1.145)
Pain0.976 (0.651, 1.465)0.641 (0.427, 0.962)0.769 (0.588, 1.005)
Weight loss0.745 (0.473, 1.172)0.771 (0.467, 1.273)0.699 (0.505, 0.969)
Back pain0.564 (0.364, 0.876)0.743 (0.486, 1.137)0.668 (0.497, 0.899)
Fatigue0.845 (0.584, 1.221)0.775 (0.525, 1.142)0.813 (0.626, 1.056)
Jaundice or yellow color or skin0.592 (0.237, 1.476)0.963 (0.461, 2.011)0.725 (0.411, 1.278)
Discomfort or pain in stomach area0.962 (0.636, 1.455)1.062 (0.705, 1.601)1.017 (0.767, 1.349)

Results

Analysis populations included REACH-2, REACH AFP ≥400 ng/mL, and the two populations pooled. FHSI-8 compliance was acceptable. Similar to REACH patients with AFP ≥400 ng/mL, RAM patients in REACH-2 reported a positive trend in TTD in FHSI-8 total score compared to PL. A similar trend was observed in most individual items, including a significant delay in back pain progression. In the pooled population, RAM treatment significantly delayed total FHSI-8 TTD, including the back pain, weight loss, and pain items, relative to PL.

Conclusions

Ramucirumab is the only agent specifically investigated in second line HCC patients with AFP >400 ng/mL to demonstrate a consistent trend for a benefit in disease-related symptoms.

Clinical trial identification

NCT02435433; NCT01140347.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Editorial Acknowledgement

Nathalie Godinot of Eli Lilly and Company provided medical writing support.

Disclosure

A.X. Zhu: Consulting or advisory role: Eisai, Bristol-Myers Squibb, Merck, Novartis, Sanofi, AstraZeneca, Bayer, Exelixis, Eli Lilly; Research funding: Eli Lilly, Bayer, Bristol-Myers Squibb, Novartis, Merck. R.S. Finn: Consulting: AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly, Pfizer, Merck, Novartis, Roche/Genentech. P.R. Galle: Consulting or advisory roles: Bayer Schering Pharma, Sirtex Medical, Eli Lilly, Bristol-Myers Squibb, MSD; Honoraria: Eli Lilly, Bristol-Meyers Squibb, Sillagen, Bayer Schering Pharma, Sirtex Medical. J.M. Llovet: Consulting: Lilly, Bayer, Bristol-Myers Squibb, Blueprint Medicines, Eisai, Celsion, Boehringer Ingelheim, Incyte; Research funding; Bayer Schering Pharma, Blueprint medicines, Boehringer Ingelheim, Incyte and Bristol-Myers Squibb. J.F. Blanc: Personal fees: Lilly, Bayer, BMS, Esai, Ipsen, Onxeo, during the conduct of the study. T. Okusaka: Research grants, Honoraria, Advisory role: Eli Lilly, Novartis Pharma K.K., Kowa K.K., Takeda, Nippon Boehringer Ingelheim, Dainippon Simitomo Pharma, Pfizer Jana, Bayer Yakuhin, Chugai Pharmaceutical, Yakuruto Honsha, Ono Pharmaceutical, Eisai, AstraZeneca, Merck Serono, OncoTherapy Science, Kyowa Hakko Kirin, Shizuoka Industry, Baxter, Nano Carrier, Zeria Pharmaceutical, Glaxo Smith Kline K.K., Nobelpharma, Bristol-Myers Squibb, Nipponchemofa, EA Pharma, Fujifilm RI Pharma, Astellas Pharma, Nippon Kayaku, Daiichi Sankyo, Celgene, MSD, Teijin Pharma. I. Chau: Advisory board: Sanofi Oncology, Eli-Lilly, Bristol-Myers Squibb, MSD, Bayer, Roche, Merck Serono, Five Prime Therapeutics; Research funding: Eli-Lilly, Janssen-Cilag, Sanofi Oncology, Merck-Serono, Novartis; Honorarium: Taiho, Pfizer, Amgen, Eli-Lilly. D. Cella: Personal fees: Lilly, during the conduct of the study, Other: FACIT.org, outside the submitted work. A. Girvan, J. Gable, L. Bowman, Y. Hsu, P.B. Abada: Employee and minor shareholder: Eli Lilly and Company. M. Kudo: Consulting or advisory role: Kowa, MSD, Bristol-Myers Squibb, Bayer, Chugai Pharma, Taiho Pharmaceutical; Honoraria: Bayer, Eisai, MSD, Ajinomoto; Research funding: Chugai Pharma, Otsuka, Takeda, Taiho Pharmaceutical, Sumitomo Dainippon, Dalichi Sankyo, MSD, Eisai, Bayer, Abbvie.

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

Invited Discussant 621PD, 622PD and One LBA TBC

Lecture Time
16:25 - 16:35
Speakers
  • Ann-Lii Cheng (Taipei, TW)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25
Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

Q&A led by Discussant

Lecture Time
16:35 - 16:45
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25
Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

LBA28 - Updated results from a phase II study of infigratinib (BGJ398), a selective pan-FGFR kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma containing FGFR2 fusions

Presentation Number
LBA28
Lecture Time
16:45 - 16:45
Speakers
  • Milind Javle (Houston, US)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

Fibroblast growth factor receptor 2 (FGFR2) fusions occur in 13–17% of intrahepatic cholangiocarcinomas (IHC). A multicenter, open-label, phase II study (NCT02150967) evaluated the antitumor activity of infigratinib, an ATP-competitive FGFR1–3-selective oral tyrosine kinase inhibitor, in patients (pts) with previously-treated advanced IHC containing FGFR2 fusions.

Methods

Pts received infigratinib 125 mg orally daily for 21 days of 28-day cycles until unacceptable toxicity, disease progression, investigator discretion, or withdrawal of consent. Primary endpoint: investigator-assessed confirmed overall response rate (cORR, RECIST 1.1). Secondary endpoints: progression-free survival (PFS), disease control rate (DCR), best overall response, overall survival (OS), safety, pharmacokinetics.

Results

71 pts (62% women; median age 53 years; median 2 prior lines of therapy) with FGFR2 fusions/translocations were included. At the prespecified data cutoff (8-Aug-2018), median duration of treatment was 5.5 months, median duration of follow-up was 8.4 months, and 62 pts had discontinued treatment. The ORR (confirmed and unconfirmed) was 31.0% (95% CI 20.5–43.1%) and the cORR (in pts with potential for confirmation) was 26.9% (95% CI 16.8–39.1%). Other efficacy findings: cORR in pts receiving ≤1 prior lines of treatment was 39.3% (n=28), and ≥2 17.9% (n=39); DCR 83.6% (95% CI 72.5–91.5%); median duration of response 5.4 (95% CI 3.7–7.4) months; median PFS 6.8 (95% CI 5.3–7.6) months; median OS 12.5 (95% CI 9.9–16.6) months. Most common any-grade treatment-emergent adverse events (TEAEs): hyperphosphatemia (73.2%), fatigue (49.3%), stomatitis (45.1%), alopecia (38.0%), constipation (35.2%). Grade 3/4 TEAEs occurred in 47 pts (66.2%), including hypophosphatemia (14.1%), hyperphosphatemia (12.7%), and hyponatremia (11.3%).

Conclusions

Infigratinib-associated toxicity is manageable, and our efficacy findings suggest clinically meaningful activity after chemotherapy in pts with IHC containing FGFR2 fusions. The efficacy of infigratinib in this study supports FGFR2 as a therapeutic target in FGFR2-fusion IHC.

Clinical trial identification

NCT02150967

Editorial Acknowledgement

Editorial assistance was provided by Lee Miller from Miller Medical Communications Ltd

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

623PD - The nationwide cancer genome screening project in Japan, SCRUM Japan GISCREEN: Efficient identification of cancer genome alterations in advanced Biliary Tract Cancer.

Presentation Number
623PD
Lecture Time
16:45 - 16:45
Speakers
  • Chigusa Morizane (Tokyo, JP)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

We initiated the Nationwide Cancer Genome Screening Project in Japan since February 2014. From October 2015, we have introduced the Next Generation Sequencing to detect cancer genome alterations in advanced biliary tract cancer (aBTC; intrahepatic bile duct, extrahepatic bile duct, gallbladder, and ampulla of Vater), called as the SCRUM-Japan GI-SCREEN. The objective is to evaluate the frequency of cancer genome alterations and to identify patients who are candidate for clinical trial with corresponding targeting agents.

Methods

This study is ongoing with 20 major cancer centers. Patients with aBTC who plan to or receive chemotherapy were eligible. DNA and RNA were extracted from formalin-fixed paraffin embedded tumor samples and were analyzed by the Oncomine Cancer Research Panel (OCP) which allows to detect mutations, copy number variant (CNV) and fusion genes in a CLIA certified CAP accredited lab. The detected genomic variant data were classified according to genetic drivers of cancer, including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase.

Results

As of March 31st 2017, a total of 167 aBTC patients were enrolled and 140 samples were analyzed. The sequence was successfully performed in 92 tumors (65.7%). The frequently detected gene alterations were shown in table. No gene fusion was detected. We will show the clinical outcome based on certain key cancer genome alterations.

IHBD n = 36EHBD 35GB 14VP 7
n(%)
TP53 mutation(m)9(25)11(31)8(57)4(57)
KRAS m12(33)11(31)2(14)4(57)
IDH1 m5(14)1(3)00
ERBB3 m1(3)3(9)1(7)0
ERBB2 m CNV ( > 7copies)0 02(6) 1(3)1(7) 1(7)0 0
CTNNB1 m1(3)1(3)1(7)2(29)
PIK3CA m004(29)1(14)
CDKN2A m3(8)02(14)0
APC m2(6)1(3)01(14)
ATM m1(3)2(6)1(7)0
FGFR3 m CNV1(3) 00 2(6)0 1(7)0 0
MDM2 CNV1(3)1(3)1(7)1(14)
SMAD4 m2(6)1(3)01(14)
STK11 m02(6)1(7)1(14)
TET2 m01(3)2(14)1(14)
CCNE1 m1(3)03(21)0

Conclusions

This nationwide screening system is efficient to detect rare gene alterations in aBTC. This novel knowledge provides an intriguing background to investigate new targeted approaches in these patients and to progress precision medicine.

Clinical trial identification

UMIN000016344. Date of disclosure of the study information2015/01/26.

Legal entity responsible for the study

SCRUM-Japan.

Funding

15 SCRUM-Japan collaborating pharmaceutical companies, AMED, NCC.

Disclosure

C. Morizane: Honoraria: Pfizer, Novartis, Yakult Honsha, Lilly, Nobelpharma, Fujifilm, Teijin Pharma, Taiho Pharmaceutical; Consulting or advisory role: Yakult Honsha, Novartis, Taiho Pharmaceutical; Research funding (to institution): Pfizer, Nobelpharma, Eisai, Yakult Honsha, Ono Pharmaceutical, Taiho Pharmaceutical. Y. Komatsu: Honoraria: Pfizer, Novartis, Bayer,Yakult Honsha, Lilly, Merck, Taiho, Takeda, Sanofi, Chugai, Ono, Asahi-kasei, Kirin-Kyowa, Nipro, Towa. H. Takahashi: Honoraria: Taiho Pharmaceutical; Research funding: Bayer Pharmaceutical, Bristol-Myers Squibb. M. Ueno: Honoraria: Taiho Pharmaceutical, Yakult Honsha, AstraZeneca, Novartis, Lilly, Teijin Pharma, Shire, Ono Pharmaceutical; Research funding: Taiho Pharmaceutical, Shire, Daiichi Sankyo, Eisai, AstraZeneca, Ono Pharmaceutical, MSD, Merck Serono, NanoCarrier, Dainippon Sumitomo Pharma, Incyte. J. Furuse: Honoraria: Taiho, Chugai, Yakult, Sumitomo Dainippon, Eli Lilly Japan, Astellas, Ono, Pfizer, Bayer, Novartis, Merck Serono, Takeda, Eisai, MSD, Shionogi, J-Pharma, Daiichi Sankyo, Mochida, Nippon Kayaku, EA pharma, Sawai, Teijin Pharma; Consulting or advisory role: Taiho, Chugai, Yakult, Sumitomo Dainippon, Eli Lilly Japan, Astellas, Ono, Pfizer, Bayer, Novartis, Merck Serono, Takeda, Eisai, MSD, Shionogi, J-Pharma, Daiichi Sankyo, Kyowa Hakko Kirin, Sanofy, Sandoz, Otsuka, Zeria, Fujifilm, AstraZeneca, Asahi Kasei, Shire; Research funding (to institution): J-Pharma, Taiho, Sumitomo Dainippon, Janssen, Daiichi Sankyo, MSD, Yakult, Takeda, Chugai, Ono, Astellas, Zeria, Novartis, Nanocarrier, Shionogi, Onco Therapy Science, Eli Lilly Japan, Bayer, Bristol-Myers Squibb, Merck Serono, Kyowa Hakko Kirin, Eisai, NanoCarrier, Mochida, Baxalta, Sanofi. T. Kudo: Research grants: Yakult Honsha, Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. S. Itoh: Speakers' bureau: Otsuka Pharmaceutical, Asahi Kasei Phama; Consulting or advisory role: Asahi Kasei Phama, Takeda; Research funding (to institution): Taiho, Sumitomo Dainippon, Daiichi Sankyo, MSD, Yakult, Chugai, Ono, Astellas, CSL Behring, Novartis, Shionogi, Eli Lilly Japan, Bayer, Merck Serono, Kyowa Hakko Kirin, Sanofy, Pfizer, Boehringer Ingelheim, Asahi Kasei Phama, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Hisamitsu Pharmaceutical, Nihon Pharmaceutical, Nihon Blood Products Organization, Kowa Company, Medtronic, Johnson and Johnson. S. Shimizu: Honoraria: Novartis, Taiho Pharmaceutical. T. Mizukami: Speakers' bureau: Taiho Pharma, Teijin Pharm. Inc., Otsuka Pharmaceutical Co., Ltd. Consulting or Advisory role: Merck Serono. S. Nomura: Honoraria: Taiho Pharmaceutical. T. Kuwata: Honoraria: Chugai Pharm, Daiichi-Sankyo; Research Funding (to institution): Daiichi-Sankyo. W. Okamoto: Grants: MSD, outside the submitted work. K. Shitara: Consulting or advisory role: Astellas Pharma, Lilly, Bristol-Myers Squibb, Takeda, Pfizer, Ono Pharmaceutical; Personal fees: Novartis, AbbVie, Yakult; Research funding (to institution): Lilly, Ono Pharmaceutical, Dainippon Sumoitomo Pharma, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharma, MSD. A. Ohtsu: Honoraria: Chugai, Ono Pharmaceuticals, BMS; Research Funding: BMS. T. Yoshino: Grants: MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., GlaxoSmithKline K.K., Nippon Boehringer Ingelheim Co., Ltd.; Grants and personal fees: Sanofi K.K., Chugai Pharmaceutical Co., Ltd, Personal fees: Eli Lilly Japan K.K, Merck Serono Co., Ltd., outside the submitted work. All other authors have declared no conflicts of interest.

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

624PD - Preliminary Results of a Ph2a Study to Evaluate the Clinical Efficacy and Safety of Erdafitinib in Asian Patients with Biomarker-Selected Advanced Cholangiocarcinoma (CCA)

Presentation Number
624PD
Lecture Time
16:45 - 16:45
Speakers
  • Yen-Yang Chen (Kaohsiung, TW)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

Advanced CCA patients (pts) who progressed after first-line chemotherapy have limited treatment options and poor prognosis. Aberrant fibroblast growth factor receptor (FGFR) signalling is a driver of the pathogenesis of CCA and is observed in 14-17% of pts. Erdafitinib, a potent oral pan-FGFR tyrosine kinase inhibitor, demonstrated encouraging clinical activity with manageable adverse events (AEs) in the Europe (EU)/United States (US) phase 1 study in solid tumours, including subjects with CCA.

Methods

LUC2001 is an open-label, multicenter, Ph2a study in advanced CCA pts with FGFR alterations, based on FoundationOne testing, who failed at least 1 prior systemic treatment. The primary endpoint is objective response rate (ORR; by RECIST 1.1). The secondary endpoints are disease control rate (DCR), safety and pharmacokinetics. Disease is evaluated every 8 weeks until disease progression (PD).

Results

As of 20 March 2018, 150 CCA pts are molecularly screened; 25 have FGFR alterations, of whom 11 (with FGFR2 fusions [7] or FGFR 2 [2] or 3 [2] mutations) are dosed with continuous 8 mg once daily erdafitinib, all response evaluable. Median age is 53.0 years, ECOG score 0 and 1 in 6 and 5 pts, respectively, 8 males and 3 females. Median number of treatment cycles is 4.0 and median treatment duration is 3.5 months. There are 3 confirmed partial response (PR), 2 unconfirmed PR (uPR), 4 stable disease (SD), and 2 PD (both with FGFR3 mutations). The ORR (CR+PR+uCR+uPR) is 45.5%. The DCR (CR+PR+uCR+uPR+SD) is 81.8%. Six pts are still on treatment. The most common AEs (>30%) are hyperphosphatemia, dry mouth, stomatitis, diarrhea, nail disorder, and palmar-plantar erythrodysaesthesia syndrome. Seven pts experienced Grade 3 or higher AEs and 3 subjects had AEs leading to dose reduction. Three pts experienced non-drug related serious AEs (SAEs), while no AE led to treatment discontinuation or death. PK characteristics are consistent with data from other studies.

Conclusions

Erdafitinib shows encouraging clinical activity and tolerable safety profile in Asian and EU/US pts with FGFR-altered advanced CCA with high unmet medical need.

Clinical trial identification

NCT02699606.

Legal entity responsible for the study

Janssen (China) Research & Development Center, a division of Johnson & Johnson (China) Investment Ltd.

Funding

Janssen APMS China Research & Development.

Disclosure

H. Liao, J. Nie, M. Qing, J. Li, P. De Porre: Employee: Janssen Research and Development; Stock ownership: Johnson&Johnson. All other authors have declared no conflicts of interest.

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

Invited Discussant LBA28, 623PD and 624PD

Lecture Time
16:45 - 16:55
Speakers
  • Ian Chau (Sutton, GB)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25
Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

Q&A led by Discussant

Lecture Time
16:55 - 17:05
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25
Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

LBA29 - CARRIE: A Randomized, Double-blind, Placebo-controlled Phase 2 Study of Istiratumab (MM-141) plus Nab-Paclitaxel and Gemcitabine versus Nab-Paclitaxel and Gemcitabine in Front-line Metastatic Pancreatic Cancer

Presentation Number
LBA29
Lecture Time
17:05 - 17:05
Speakers
  • Andrew H. Ko (San Francisco, US)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

High serum IGF-1 levels have been associated with more aggressive pancreatic cancer (PDAC). Pre-clinical data suggest that dual blockade of the IGF-1 and HER3 pathways has superior activity to IGF-1 blockade alone in PDCA. We tested whether istiratumab, an IGF-1R and ErbB3 bi-specific antibody, can enhance the efficacy of standard of care (SOC) chemotherapy in patients with high serum IGF-1 levels.

Methods

CARRIE was a randomized, double-blind, placebo-controlled, international Phase 2 study of nab-paclitaxel/gemcitabine alone or in combination with istiratumab in front-line metastatic PDAC. In Part 1, 10 patients were evaluated for PK and safety. In Part 2, patients with high free serum IGF-1 levels were randomized 1:1 to receive either istiratumab (2.8 g. IV Q2W) or placebo plus nab-paclitaxel/gemcitabine at the approved dose schedule. Heregulin (HRG) was tested in pre-treatment tumor samples. The co-primary endpoints were Progression Free Survival (PFS) in patients with high IGF-1 levels and in patients with both high IGF-1 levels and HRG+ tumors. Key secondary endpoints included Overall Survival (OS), Objective Response Rate (ORR) by RECIST v1.1, and adverse events (AEs) rate.

Results

A total of 317 patients were screened to enroll 88 patients (experimental arm n=43; control n=45) in Part 2. In the high IGF-1 cohort, median PFS was 3.6 and 7.3 months in the experimental vs. control arms, respectively (HR=1.88, p=0.027). In the combined high IGF-1/HRG+ subgroup (n=44), median PFS was 4.1 and 7.3 months, respectively (HR=1.39, p=0.42). Median OS and ORR for the overall population were similar between two arms (8.9 and 11.7 months, HR=1.36, p=0.22 and 39.5 vs. 51.2%, p=0.33, respectively). No significant difference in serious or Grade > 3 AEs was observed, although low-grade AEs leading to early discontinuation were higher in the experimental (39.5%) vs. control arm (24.4%).

Conclusions

Istiratumab failed to improve the efficacy of SOC chemotherapy in the front-line treatment of patients with metastatic PDAC and high IGF-1. High serum IGF-1 levels did not appear to be an adverse prognostic factor in this setting.

Clinical trial identification

Clinical trial information: NCT02399137.

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

625PD - Pembrolizumab for advanced biliary adenocarcinoma: Results from the multicohort, phase 2 KEYNOTE-158 study

Presentation Number
625PD
Lecture Time
17:05 - 17:05
Speakers
  • Makoto Ueno (Yokohama, JP)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

Biliary tract cancers (BTC) are often diagnosed at an advanced stage, with standard gemcitabine plus cisplatin combination chemotherapy providing limited benefit. The phase 2, multicohort KEYNOTE-158 study (NCT02628067) evaluated antitumor activity and safety of pembrolizumab (pembro), an anti–PD-1 antibody in patients (pts) with advanced BTC.

Methods

Pts aged ≥18 y with histologically/cytologically confirmed unresectable or metastatic BTC and prior progression/intolerance on standard therapy were enrolled if they had measurable disease per RECIST v1.1, ECOG PS ≤ 1, and tumor sample for evaluation of PD-L1 (PD-L1 IHC 22C3 pharmDx assay [Agilent Technologies]) and other biomarkers. Pts received pembro 200 mg Q3W for up to 2 y or until disease progression or unacceptable AEs. The primary endpoint was ORR; DOR, PFS, OS and safety were secondary endpoints. Response was assessed every 9 wks in year 1, then every 12 wks (RECIST v1.1, independent central review). DOR, PFS, and OS were evaluated using the Kaplan-Meier method. AE severity was graded per NCI CTCAE v4.0. PD-L1 combined positive score (CPS; ≥1 or < 1) was determined.

Results

At data cutoff (Jan 15, 2018), 104 pts with BTC (49% male; median age, 63 y [range, 34–81]; ≥2 prior therapies, 52%) were enrolled (median follow-up, 9.3 mo [range, 0.6–23.6]). ORR was 5.8% (95% CI, 2.1–12.1; 6 PR, 0 CR); 17 pts (16%) had SD. Median DOR was not reached (range, 6.2–15.7+ mo); 2 pts had DOR ≥15 mo. ORR was 6.6% (95% CI, 1.8–15.9) and 2.9% (95% CI, 0.1–15.3) among those with PD-L1 CPS ≥1 (n = 61) and CPS <1 (n = 34), respectively. Median PFS was 2.0 mo (95% CI, 1.9–2.1) and median OS was 9.1 mo (95% CI, 5.6–10.4). Median PFS was 1.9 mo (95% CI, 1.8–2.0) vs 2.1 mo (95% CI, 1.9–2.6) and median OS was 7.2 mo (95% CI, 5.3–11.0) vs 9.6 mo (95% CI, 5.4–12.8) among pts with PD-L1 CPS ≥1 vs < 1, respectively. 99 pts (including all responders) were evaluated for MSI status; none were MSI-H. Overall, 55% of pts had treatment-related AEs (most commonly fatigue [14%], rash [12%], pruritus [9%]); 13% had grade 3–5 AEs, and 16% had immune-mediated AEs. Treatment-related AEs led to discontinuation in 6 pts.

Conclusions

Pembro shows durable antitumor activity in a subset of pts with advanced BTC regardless of PD-L1 CPS and had manageable toxicity.

Clinical trial identification

NCT02628067.

Legal entity responsible for the study

Merck Sharp & Dohme Corp.

Funding

Merck Sharp & Dohme Corp.

Editorial Acknowledgement

Medical writing and editorial assistance was provided by Sheri Arndt, PharmD, of C4 MedSolutions, LLC (Yardley, PA), a CHC Group company. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

M. Ueno: Honoraria and research funding: Taiho Pharmaceutical, Shire, AZ; Honoraria: Yakult Honsha, Novartis, Lilly, Teijin Pharma, Ono Pharmaceutical (OP); Research funding: Daiichi Sankyo, Eisai, OP, MSD, Merck Serono, NanoCarrier, Dainippon Sumitomo Pharma, Incyte. H.C. Chung: Consultant/advisor: Taiho, Celltrion, MSD, Lilly, Quintiles, BMS, Merck-Serono; Speaker: Merck-Serono, Lilly, Foundation Medicine; Research funding: Lilly, GSK, MSD, Merck-Serono, BMS-Ono, Taiho. A. Nagrial: Consultant/advisor for MSD, AstraZeneca, Shire; Speaker: AstraZeneca, Roche, BMS, MSD. A. Marabelle: Honoraria: Merck, BMS, Roche, Genentech; Research funding: Merus; Travel/accommodation: Roche, BMS, Amgen; Consultant/advisor: Roche, Genentech, Novartis, Amgen; Speaker: BMS, Amgen, Roche, Merck. R.K. Kelley: Advisory board: Bayer, Debiopharm Group; Steering committee: Agios, AZ, BMS; Research funding: Lilly, Exelixis, Regeneron, Celgene, Tekmira, Sanofi, Novartis, BMS, MedImmune, MSD, Agios, AZ, Adaptimmune, Taiho Pharmaceutical, Target Pharmasolutions, Bayer. L. Xu, S.K. Pruitt: Employee: Merck Sharp & Dohme Corp. J. Mahoney: Employee: ExecuPharm, King of Prussia, PA, USA, working under contract at Merck Sharp & Dohme Corp. D-Y. Oh: Research funding: AstraZeneca.

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

626PD - Randomized, Phase III Trial Comparing Adjuvant Gemcitabine (Gem) versus Gem plus Chemoradiation (CCRT) in Curatively Resected Pancreatic Ductal Adenocarcinoma (PDAC) – A Taiwan Cooperative Oncology Group Study

Presentation Number
626PD
Lecture Time
17:05 - 17:05
Speakers
  • Hui-Ju Chang (Tainan, TW)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25

Abstract

Background

Adjuvant chemotherapy is the standard of care for PDAC after curative intent surgery. Current study aims to evaluate the role of additional consolidation CCRT to 6-month adjuvant Gem therapy in resectable PDAC.

Methods

Patients with R0/R1 resected PDAC, and negative CT finding within 2 weeks and CA-19.9 <2.5x NUL within one week before registration were eligible. Enrolled patients were stratified by section margin, tumor size and lymph node status then randomized to have either 6 cycles of weekly gemcitabine, day 1, 8 and 15 every 28 days (Arm 1) or 3 cycles of weekly Gem followed by Gem-based CCRT and then another 3 cycles of Gem (Arm 2). The treatment should be initiated within 8 weeks after surgery. The primary end-point was recurrence-free survival (RFS). Secondary end points were overall survival (OS), progression pattern, safety profile and quality of life.

Results

Between 2009 and 2015, 147 patients were included, 74 in Arm 1 and 73 in Arm 2. With a minimum of 2 years follow-up, the median RFS was similar between Arm 1 and Arm 2: 12.1(95% CI, 9·0-15·8) versus 13.3 (95% CI, 10.0-17.1) months, (hazard ratio 0.96 [95% CI, 0·67-1·37, p = 0.80]); while OS was 23·5 (95% CI, 18·1-30.8) versus 21·5 (95% CI, 16·7-28·1) months, (hazard ratio 1.07 [95% CI, 0·74-1·55, p = 0·73]). Local recurrence rate was marginally less in Arm 2 (17.6% vs 15.1%, p = 0·68). Grade 3/4 toxicity was 66% vs 73% in Arm 1 and 2, respectively, p = 0·34. Patients in Arm 1 had a trend of better global health status, p = 0·12.

Conclusions

This is the first randomized trial using survival as primary endpoint to evaluate the role of add-on CCRT for curatively resected PDAC receiving standard, adjuvant Gem therapy. Despite a trend of better loco-regional control, the add-on CCRT did not improve the RFS and OS in such a patient population. Systemic chemotherapy should remain as the standard of care for PDAC after curative-intent surgery.

Clinical trial identification

NCT00994721.

Legal entity responsible for the study

Taiwan Cooperative Oncology Group.

Funding

National Health Research Institutes.

Disclosure

J-S. Chen: Research funding: Ono Pharmaceutical, MSD Oncology, MedImmune, Lilly, TTY Biopharm, Daiichi Sankyo, Orient EuroPharma. L-T. Chen: Research funding: Novartis, Merck, Serono, TTY, Polaris, SyncorePharm, Pfizer, BMS; Honoraria: Ono, Eli Lilly, MSD, PharmaEngine, TTY, SyncorePharm, Novartis, Astra Zeneca, Ipsen; Patents & Royalties of ENO-1mAb/HuniLife; Membership on board of directors or advisory committes: PharmaEngine. All other authors have declared no conflicts of interest.

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Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

Invited Discussant LBA29, 625PD and 626PD

Lecture Time
17:05 - 17:15
Speakers
  • Eileen M. O'Reilly (New York, US)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25
Poster Discussion session -Gastrointestinal, non-colorectal Poster Discussion session

Q&A led by Discussant

Lecture Time
17:15 - 17:25
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
19.10.2018
Time
15:45 - 17:25