Channel 1 Proffered Paper session
Date
19.09.2020
Time
14:25 - 16:05
Room
Channel 1
Chairs
  • Michel P. Ducreux (Villejuif, CEDEX, France)
  • Chiara Cremolini (Pisa, Italy)
Proffered Paper - GI, colorectal Proffered Paper session

396O - Health-related quality of life (HRQoL) in patients (pts) treated with pembrolizumab (pembro) vs chemotherapy as first-line treatment in microsatellite instability-high (MSI-H) and/or deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC): Phase III KEYNOTE-177 study

Presentation Number
396O
Lecture Time
14:25 - 14:37
Speakers
  • Thierry AndrĂ© (Paris, CEDEX 12, France)
Room
Channel 1
Date
19.09.2020
Time
14:25 - 16:05

Abstract

Background

Pembro monotherapy significantly improved PFS vs standard of care (SOC) chemotherapy as first-line treatment in pts with MSI-H or dMMR mCRC in the phase III KEYNOTE-177 (NCT02563002) study. HRQoL results are reported.

Methods

Pts with confirmed MSI-H/dMMR mCRC with no prior systemic therapy for mCRC were randomized 1:1 to pembro 200 mg Q3W for up to 2 y or investigator’s SOC choice of mFOLFOX6 or FOLFIRI Q2W ± bevacizumab or cetuximab. EORTC QLQ-C30, EORTC QLQ-CR29, and EQ-5D-3L were administered at baseline and at various time points up to 1 y or end of treatment, whichever came first, and at 30 days after treatment discontinuation. Data from pts receiving ≥1 dose of study treatment and completing ≥1 HRQoL assessment were analyzed. Least-squares mean (LSM) score change from baseline to prespecified wk 18, 95% CI, and nominal 2-sided P values were calculated. Time to deterioration (TTD; ≥10-point decline from baseline) was assessed by Kaplan-Meier method and Cox regression model. HRs, 95% CIs, and nominal 1-sided P values are provided.

Results

Data for 294 pts (152, pembro; 142 SOC) were available for HRQoL analyses. Compliance at baseline was >90% in pembro and SOC arms for all 3 questionnaires and remained high at wk 18 (>85% and >75%, respectively). LSM change from baseline to wk 18 showed clinically meaningful improvement in QLQ-C30 global health status (GHS)/QoL (LSM difference: 8.96; 95% CI, 4.24-13.69; P=0.0002) and EQ-5D VAS (LSM difference: 7.38; 95% CI, 2.82-11.93; P=0.0016) for pts receiving pembro vs SOC. Prolonged TTD for pts receiving pembro vs SOC was observed for GHS/QoL (HR, 0.61; 95% CI, 0.38-0.98; P=0.0195), physical functioning (HR, 0.50; 95% CI, 0.32-0.81; P=0.0016), social functioning (HR, 0.53; 95% CI, 0.32-0.87; P=0.0050), and fatigue (HR, 0.48; 95% CI, 0.33-0.69; P≤0.0001).

Conclusions

Pembro monotherapy demonstrated clinically meaningful improvements in HRQoL vs SOC chemotherapy in pts with previously untreated MSI-H/dMMR mCRC.

Clinical trial identification

NCT02563002.

Editorial acknowledgement

Medical writing and/or editorial assistance provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA) and funded by Merck Sharp & Dohme Corp.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

T. André: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol Myers-Squibb; Honoraria (self): Chugai; Honoraria (self): GSK; Honoraria (self): Pierre Fabre; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/Vantana; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Servier; Advisory/Consultancy: Amgen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Gritstone Oncology; Advisory/Consultancy: Halliodx; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme Corp; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Tesaro; Non-remunerated activity/ies, Participant of the Scientific committee : ARCAD foundation and GERCOR group. M. Amonkar: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. J. Norquist: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. K-K. Shiu: Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self): Guardant Health; Honoraria (self): Innovent Biologics; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck KGaA; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self): Servier; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Gilead; Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Innovent Biologics. T.W. Kim: Research grant/Funding (institution): Merck Serono, AstraZeneca, Pfizer. B.V. Jensen: Research grant/Funding (institution): Merck Sharp & Dohme Corp.. L.H. Jensen: Research grant/Funding (institution): MSD; Research grant/Funding (institution): 2cureX; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): BMS. C.J. Punt: Advisory/Consultancy: Bayer; Advisory/Consultancy: Nordic Pharma; Advisory/Consultancy: Servier. R. Garcia-Carbonero: Honoraria (self), Speaker Bureau/Expert testimony: AAA, Advanz Pharma, Bayer, BMS, HMP, Ipsen, Merck, Midatech Pharma, MSD, Novartis, PharmaMar, Pfizer, Pierre Fabre, Roche, Sanofi and Servier; Research grant/Funding (self), Financial support to an investigator-initiated trial evaluating Axitinib in NETs and Nivolumab in NECs: Pfizer, BMS; Research grant/Funding (institution), Institutional support for the conduct of clinical trials or for molecular diagnostic platforms: ARMO Biosciences, Astrazeneca, Pfizer, Novartis, Ipsen, Roche, Pharmacyclics, Boston Biomedicals, Merck, MSD, Amgen, Sanofi, Bayer, Bristol-Myers-Squibb, Boerhringer, Sysmex, Gilead Sciences, Servier, Adacap, VCN, Lilly, Pharmamar; Leadership role, Non-remunerated activity/ies, Member of the Executive Committee of the Spanish Neuroendocrine Tumor Cooperative Group (GETNE), Member of the Executive Committee of the European Society of Neuroendocrine Tumors (ENETS), Member of the Scientific Advisory Group for Oncology (SAG-O) of the European Medicines Agency (EMA) (2008-2017): GETNE, ENETS, SAG-O, EMA. I. Sevilla: Advisory/Consultancy: Ipsen, Pfizer, Syrtex, Amgen, Pharmamar; Speaker Bureau/Expert testimony: AAA, Sanofi, Novartis. C. de la Fouchardiere: Advisory/Consultancy: Roche, Pierre Fabre Oncologie, MSD, Eisai, Bayer; Travel/Accommodation/Expenses: Amgen, Eisai, BMS, Roche. F. Rivera: Advisory/Consultancy: MSD, Roche, Merck-Serono, Sanofi, BMS, Servier, Lilly, Amgen, Bayer, Celgene; Travel/Accommodation/Expenses: MSD, Roche, Merck-Serono, Sanofi, BMS, Servier, Lilly, Amgen, Bayer, Celgene. E. Elez: Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Hoffmann-La Roche, Servier, Amgen, Array Biopharma, Sanofi, Merck Sharp & Dohme Corp.; Research grant/Funding (institution): Array Biopharma, Merck Sharp & Dohme Corp., AbbVie, Amgen, GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Novartis, Boehringer Ingelheim, Hoffmann-La Roche; Research grant/Funding (self): Merck Sharp & Dohme Corp., Sanofi. L.A. Diaz: Advisory/Consultancy: Merck, Caris, Lyndra, Genocea Biociences, Illumina, Cell Design Labs, Neophore; Leadership role, Shareholder/Stockholder/Stock options, Officer/Board of Directors: PGDx; Shareholder/Stockholder/Stock options: Thrive, Neophore; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Licensing/Royalties: Multiple, managed by Johns Hopkins and MSKCC COI; Officer/Board of Directors: Jounce Therapeutics; Spouse/Financial dependant: Amgen (equity). T. Yoshino: Research grant/Funding (institution): Novartis Pharma K.K.; Research grant/Funding (institution): MSD K.K.; Research grant/Funding (institution): Sumitomo Dainippon Pharma Co., Ltd.; Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Research grant/Funding (institution): Sanofi K.K.; Research grant/Funding (institution): Daiichi Sankyo Company, Limited; Research grant/Funding (institution): Parexel International Inc.; Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd.; Research grant/Funding (institution): GlaxoSmithKline K.K.. E. Van Cutsem: Advisory/Consultancy: Array, Astrazeneca, Bayer, Biocartis, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Pierre-Fabre, Roche, Servier, Sirtex, Taiho; Research grant/Funding (institution): Bayer, Boehringer Ingelheim, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier paid to the institution . P. Yang: Full/Part-time employment: MSD China Holding Co., Ltd.. M.Z.H. Farooqui: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. D. Le: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Research grant/Funding (self): BMS; Research grant/Funding (self): Aduro; Research grant/Funding (self): Medivir; Research grant/Funding (self): Curegenix; Research grant/Funding (self): Nouscom. All other authors have declared no conflicts of interest.

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Proffered Paper - GI, colorectal Proffered Paper session

397O - Avelumab plus cetuximab in pre-treated RAS wild type metastatic colorectal cancer patients as a rechallenge strategy: The phase II CAVE (cetuximab-avelumab) mCRC study

Presentation Number
397O
Lecture Time
14:37 - 14:49
Speakers
  • Erika Martinelli (Napoli, Italy)
Room
Channel 1
Date
19.09.2020
Time
14:25 - 16:05

Abstract

Background

Rechallenge strategies with anti-epidermal growth factor receptor (EGFR) drugs have been evaluated in patients (pts) with refractory RAS/BRAF wild type (WT) mCRC after response to anti-EGFR based 1st line therapy. Given the role of cetuximab in enhancing antibody-dependent cellular cytotoxicity (ADCC) and promoting expression of MHC class II molecules on dendritic cells, its association with anti-PD-L1 avelumab may be a relevant rechallenge strategy in RAS WT mCRC.

Methods

CAVE mCRC, a single arm multi-centre phase II study, aims to evaluate the efficacy of avelumab and cetuximab in RAS WT mCRC pts treated in first line with chemotherapy (CT) in combination with anti-EGFR drugs and who achieved a complete (CR) or partial response (PR). Primary endpoint is median overall survival (mOS), secondary endpoints are overall response rate (ORR) according to RECIST 1.1, progression free survival (PFS) and safety profile. This study seeks to demonstrate a mOS of 11 months (mo) for the experimental combination in comparison with historical mOS of 8.0 mo with standard third line treatments, which corresponds to an improvement in mOS of 37,5 %.

Results

From August 10, 2018 to February 21, 2020, 77 pts have been enrolled and started treatment with avelumab 10 mg/kg q14 and cetuximab at 400 mg/m2 and subsequently 250 mg/m2 weekly until progression of disease (PD) or unacceptable toxicity. Kaplan-Meier curves estimated for the whole intention-to-treat (ITT) population (77 pts): mOS was 13.1 mo (95% Confidence Interval CI, 7.4-18.8 mo; 32 events); mPFS, 3.6 mo (95% CI, 3.3-3.9 mo; 62 events). Among 65 pts evaluable for response, 1 pt (1.5%) experienced CR, 3 pts (4.6%) PR, 32 pts stable disease (SD) (49.2%); 29 pts PD (44.6%). Pts with PFS≥ 6 mo were 12/65 (18.5%). Grade-3 adverse events were reported in 16/77 pts (22%), the most common being skin rash 10/77 (13%) and diarrhoea 3/77 (4%).

Conclusions

At this preliminary analysis, avelumab plus cetuximab as a rechallenge strategy is effective and well tolerated in chemorefractory RAS/BRAF WT mCRC pts. The final analysis for OS will be presented at the ESMO 2020 congress.

Clinical trial identification

EudraCT 2017-004392-32.

Legal entity responsible for the study

Department of Precision Medicine, Università degli Studi della Campania \"L. Vanvitelli\".

Funding

Merck.

Disclosure

E. Martinelli: Advisory/Consultancy: Amgen, Bayer, Merck-Serono, Roche, Sanofi, Servier, Pierre Fabre. T. Troiani: Advisory/Consultancy: Roche, Merck, Sanofi, Servier, Novartis, Bayer. F. Pietrantonio: Advisory/Consultancy: Amgen, Roche, Lilly, Sanofi, Merck-Serono, Bayer, Servier; Research grant/Funding (self): BMS. A. Avallone: Advisory/Consultancy: Amgen ; Speaker Bureau/Expert testimony: Servier . N. Normanno: Advisory/Consultancy: MSD, Qiagen, Biocartis, Incyte, Roche, BMS, MERCK, Thermofisher,Boehringer Ingelheim, Astrazeneca, Sanofi, Eli Lilly, Bayer. E. Maiello: Advisory/Consultancy: Astra Zeneca, Eli Lilly, Servier, Sanofi Genzyme, Roche, Merck, Eisai, Pfizer. A. Falcone: Advisory/Consultancy: Bayer, Bristol, Eli Lilly, Merck, Pierre-Fabre, Roche, Servier, and institutional support for clinical trials from Astra-Zeneca, Bayer, Bristol, Eli Lilly, Merck, MSD, Novartis, Roche, Sanofi, and Servier. C. Pinto: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS, MSD, Bayer, Astra-Zeneca, Roche, Merck, Lilly, Servier, Sanofi, Astellas. F. Ciardiello: Advisory/Consultancy: Roche, Amgen, Merck, Pfizer, Sanofi, Bayer, Servier, BMS, Cellgene, Lilly; Research grant/Funding (self): Bayer, Roche, Merck, Amgen, AstraZeneca, Takeda. All other authors have declared no conflicts of interest.

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Proffered Paper - GI, colorectal Proffered Paper session

Invited Discussant 396O and 397O

Lecture Time
14:49 - 14:59
Speakers
  • Chiara Cremolini (Pisa, Italy)
Room
Channel 1
Date
19.09.2020
Time
14:25 - 16:05
Proffered Paper - GI, colorectal Proffered Paper session

Q&A and live discussion

Lecture Time
14:59 - 15:09
Speakers
  • Michel P. Ducreux (Villejuif, CEDEX, France)
Room
Channel 1
Date
19.09.2020
Time
14:25 - 16:05
Proffered Paper - GI, colorectal Proffered Paper session

398O - Effect of 5 years of imaging and CEA follow-up to detect recurrence of colorectal cancer (CRC) - PRODIGE 13 a FFCD phase III trial

Presentation Number
398O
Lecture Time
15:09 - 15:21
Speakers
  • Come Lepage (Dijon, Cedex, France)
Room
Channel 1
Date
19.09.2020
Time
14:25 - 16:05

Abstract

Background

Intensive follow-up of patients (pts) after curative surgery for CRC is recommended by various scientific societies. These recommendations are mainly based on expert opinions and results of the few clinical trials performed are controversial. Moreover, no survival benefit has been demonstrated.

Methods

PRODIGE 131 is a prospective multicentre controlled trial evaluating by double randomisation the impact of i) intensive radiological monitoring (CT-scan/6m) versus a standard one (abdominal ultrasound/3m and thoracic radiography/6m) and ii) CEA assessment versus no, in the follow-up of resected stage II or III CRC with no evidence of residual disease on post-surgical investigation in France and Belgium. The primary endpoint was 5-year overall survival (OS).

Results

Between 09/2009 and 04/2015, 1995 pts were included (75.9%< 75 years old, 16% rectal, 44% left colon cancer (CC)). Among CC 52 % were Stage II (25% received adjuvant chemotherapy). With a median follow-up of 6.5 years, cancer recurrence was detected in 22% of the cases and second CRC in 1.7%. Among recurrences in CC, 8.4% were localized, 74.7% metastatic, and 15.7% both. These pts were treated with curative intent, respectively in 86.7%, 52.3% & 44.6%. Surgical treatment of recurrence with curative intent was 40.9% in the minimum follow-up group (No CEA & standard imaging), 66.3% in the CEA & standard imaging group, 50.7% in the No CEA & CT, and 59.5% in the maximum follow-up group (CEA & CT) (p=0.0035). Among recurrences in rectal cancer, 19.3% were localized, 65% metastatic, and 15.7% both. These pts were treated with curative intent, respectively in 50%, 53.7% & 38.5%. Surgical treatment of recurrence with curative intent was 42.9% in the minimum follow-up group, 57.9% in the CEA group & standard imaging, 55% in the No CEA & CT, and 47.8% in the maximum follow-up group (NS). None of the follow-up modalities resulted in a difference in OS (2nd interim analysis - 455 events).

Conclusions

After curative surgery, the addition of CEA and/or CT does not provide any benefit in 5-year OS, but allows more curative intent secondary surgeries for patients with a more intensive follow-up. Final results of the study will be reported at the meeting. Ref: (1) Lepage Dig Liver Dis. 2015.

Clinical trial identification

NCT00995202.

Legal entity responsible for the study

FFCD.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Proffered Paper - GI, colorectal Proffered Paper session

399O - Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in elderly patients: A subgroup analysis from TOSCA trial

Presentation Number
399O
Lecture Time
15:21 - 15:33
Speakers
  • Sara Lonardi (Padova, Italy)
Room
Channel 1
Date
19.09.2020
Time
14:25 - 16:05

Abstract

Background

Previous studies stating the combination of oxaliplatin and fluoropyrimidines as the standard of care for the adjuvant therapy of stage III colon cancer (CC) patients (pts) obtained non-convergent results and a reduced benefit for those over the age of 70 years.

Methods

We have assessed the impact of age (categorized as < or ≥ 70 years) on relapse free interval (RFI), defined as time from random to relapse or last disease assessment, in stage III CC pts randomized to receive 3 or 6 months of FOLFOX (FULV plus oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) in the Italian, multicenter, phase III, TOSCA study (clinicaltrials.gov NCT0064660).

Results

3,759 pts were enrolled from 130 sites. Overall, 2,360 of them had stage III disease, including 1,667 aged under 70 and 693 aged 70 or over. The elderly had an ECOG performance status (PS) more often equal to 1 (10.5% vs 3.3%, p <0.001), fewer women (40.8% vs 45.1, p=0.057), more T3/T4 tumors (90.9% vs 84.3%, p<0.001), a greater number of poorly differentiated (G3) tumors (28.3% vs 24.2%, p=0.039) and located on the right (40.9% vs 26.6%, p <0.001). No variation for type and treatment arm (p=0.965) was observed. The median follow-up was 62.5 and 60.6 months for the under 70 and the over 70, respectively. In pts over 70, we found a greater proportion of dose reductions (46.7% vs 41.4%, p=0.018), treatment interruptions (26.1% vs 19.3%, p<0.001) and a higher proportion of recurrences (24.2% vs 20.3%, p=0.033). The multivariable analysis of the RFI, corrected for sex, ECOG PS, tumor site, stage, grade, treatment, treatment duration and dose reduction, does not indicate a statistically significant effect of age (HR 1.19, 95% CI 0.98-1.44, p=0.082), although the point estimate is not negligible. Only a stage III high risk CC had a significant impact on RFI (HR [vs low risk] 2.05, 95% CI 1.71-2.46, p<0.001).

Conclusions

Comparing to younger pts, in elderly stage III CC pts treated with an oxaliplatin-based adjuvant therapy, a different treatment tolerability and a potential reduction of benefit was highlighted. Considerations should be made about the patient's general health status, his comorbidities and the management of the expected side effects.

Legal entity responsible for the study

GISCAD.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Proffered Paper - GI, colorectal Proffered Paper session

Invited Discussant 398O and 399O

Lecture Time
15:33 - 15:43
Speakers
  • Timothy J. Price (Woodville, SA, Australia)
Room
Channel 1
Date
19.09.2020
Time
14:25 - 16:05
Proffered Paper - GI, colorectal Proffered Paper session

Q&A and live discussion

Lecture Time
15:43 - 15:53
Speakers
  • Michel P. Ducreux (Villejuif, CEDEX, France)
Room
Channel 1
Date
19.09.2020
Time
14:25 - 16:05