Displaying One Session

Salamanca Auditorium (Hall 3) Proffered Paper session
Date
29.09.2019
Time
15:00 - 16:05
Location
Salamanca Auditorium (Hall 3)
Chairs
  • Joaquin Mateo (Barcelona, Spain)
  • Ruth Plummer (Newcastle upon Tyne, Tyne and Wear, United Kingdom)
Proffered Paper session: Genomic characterization of cancer cells to guide precision medicine: Next steps Proffered Paper session

Introduction (ID 7288)

Lecture Time
15:00 - 15:05
Speakers
  • Joaquin Mateo (Barcelona, Spain)
Location
Salamanca Auditorium (Hall 3), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
15:00 - 16:05
Proffered Paper session: Genomic characterization of cancer cells to guide precision medicine: Next steps Proffered Paper session

LBA26 - Pan-cancer whole genome analyses of metastatic solid tumors (ID 7183)

Presentation Number
LBA26
Lecture Time
15:05 - 15:20
Speakers
  • Edwin Cuppen (Amsterdam, Netherlands)
Location
Salamanca Auditorium (Hall 3), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
15:00 - 16:05

Abstract

Background

Metastatic cancer is one of the major causes of death and is associated with poor treatment efficiency. A better understanding of the characteristics of late stage cancer is required to help tailor personalised treatment, reduce overtreatment and improve outcomes.

Methods

Here we describe the largest pan-cancer study of metastatic solid tumor genomes, including 2,520 whole genome-sequenced tumor-normal pairs, analyzed at a median depth of 106x and 38x respectively, and surveying over 70 million somatic variants.

Results

Metastatic lesions were found to be very diverse, with mutation characteristics reflecting those of the primary tumor types, although with high rates of whole genome duplication events (56%). Metastatic lesions are relatively homogeneous with the vast majority (96%) of driver mutations being clonal and up to 80% of tumor suppressor genes bi-allelically inactivated through different mutational mechanisms. For 62% of all patients, genetic variants that may be associated with outcome of approved or experimental therapies were detected. These actionable events were distributed over the various mutation types (single and multiple nucleotide variants, insertions and deletions, copy number alterations and structural variants) underlining the importance of comprehensive genomic tumor profiling for cancer precision medicine for advanced cancer treatment.

Conclusions

Whole genome sequencing on fresh biopsies of metastatic cancer is feasible and identifies not only new insights in genome biology but also new opportunities for patients with both approved and experimental agents. We have created the largest data base of whole genome sequenced metastatic cancer patients which continues to facilitate new precision medicine studies.

Legal entity responsible for the study

The authors.

Funding

Hartwig Medical Foundation, Barcode for Life, Dutch Cancer Society.

Disclosure

E. Cuppen: Honoraria (self), Advisory / Consultancy: InteRNA technologies BV; Honoraria (institution), Advisory / Consultancy: Illumina; Full / Part-time employment, Officer / Board of Directors: Hartwig Medical Foundation. M.P. Lolkema: Advisory / Consultancy: Incyte; Advisory / Consultancy: Amgen; Advisory / Consultancy: Janssen Cilag BV; Advisory / Consultancy: Bayer; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi Aventis Netherlands BV. P. Roepman: Honoraria (institution), Advisory / Consultancy: Illumina. V.C.G. Tjan-Heijnen: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: E. Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca. C. van Herpen: Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Ipsen ; Advisory / Consultancy: MSD; Advisory / Consultancy: Regeneron; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): BMS ; Research grant / Funding (self): MSD; Research grant / Funding (self): Merck; Research grant / Funding (self): Ipen; Research grant / Funding (self): Novartis ; Research grant / Funding (self): Sanofi . E.F. Smit: Honoraria (institution): AstraZeneca ; Honoraria (institution): BMC; Honoraria (institution): Bayer; Honoraria (institution): Eli Lilly ; Honoraria (institution): MSD; Honoraria (institution): Merck ; Honoraria (institution): Novartis; Honoraria (institution): Pfizer; Honoraria (institution): Takeda; Honoraria (institution): Regeneron; Honoraria (institution): Roche ; Honoraria (institution): Seattle Genetrics; Advisory / Consultancy: Eli Lilly ; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Merck; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.

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Proffered Paper session: Genomic characterization of cancer cells to guide precision medicine: Next steps Proffered Paper session

LBA27 - Drug Rediscovery Protocol: Expanded use of existing anticancer drugs (ID 7182)

Presentation Number
LBA27
Lecture Time
15:20 - 15:35
Speakers
  • Emile E. Voest (Amsterdam, Netherlands)
Location
Salamanca Auditorium (Hall 3), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
15:00 - 16:05

Abstract

Background

Large-scale genetic tumor profiling can identify increasing numbers of potentially actionable molecular variants for which approved anti-cancer drugs are available. In daily practice, however, when patients with such variants are treated with drugs outside of their approved label, successes and failures are not systematically collected or shared.

Methods

We initiated the Drug Rediscovery Protocol (DRUP), an innovative and adaptive precision oncology trial aimed at identifying signals of activity in cohorts of patients with defined tumor types and molecular variants, treated with anti-cancer drugs outside their approved label. Eligible patients have exhausted (or declined) standard therapies and have malignancies with potentially actionable variants for which no approved anti-cancer drugs are available.

Results

Here, we show an overall clinical benefit rate (defined as complete or partial response, or stable disease ≥16 weeks) of 34% in the first 215 treated patients. This comprised 136 patients who received targeted therapies, and 79 patients who received immunotherapy. Overall median clinical benefit duration was nine months (95% CI 8 – 11 months), including 26 patients with ongoing clinical benefit at data cutoff. The potential of DRUP was illustrated by the identification of a successful cohort of patients with microsatellite instable tumors receiving nivolumab, and a cohort of colorectal cancer patients with relatively low mutational load with limited clinical benefit from immunotherapy.

Conclusions

The DRUP hereby facilitates defined use of approved drugs beyond their label in (rare) cancer subgroups, identifies early signals of activity in these subgroups, accelerates clinical translation of new insights, and creates a publicly available knowledge-base for future decision making.

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

Hartwig Medical Foundation, Dutch Cancer Society, Barcode for Life, Roche, Novartis, MSD, GSK, Pfizer, AstraZeneca, BMS.

Disclosure

E.E. Voest: Research grant / Funding (self), Legally responsible for all contracts: All pharma. C. van Herpen: Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self): Ipsen; Advisory / Consultancy, Research grant / Funding (self): MSD; Advisory / Consultancy: Regeneron; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Merck; Research grant / Funding (self): Novartis; Research grant / Funding (self): Sanofi. M. Chalabi: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Netherlands Cancer Institute. E.F. Smit: Honoraria (institution), Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (institution): Bayer; Honoraria (institution), Advisory / Consultancy: Eli Lilly; Honoraria (institution), Research grant / Funding (institution): MSD; Honoraria (institution), Research grant / Funding (institution): Merck; Honoraria (institution): Novartis ; Honoraria (institution): Pfizer; Honoraria (institution): Takeda; Honoraria (institution): Regeneron; Honoraria (institution), Research grant / Funding (institution): Roche Genentech; Honoraria (institution): Seattle Genetics. N. Mehra: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution): Janssen-Cilag; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Research grant / Funding (institution): Sanofi. E. Cuppen: Honoraria (institution), Advisory / Consultancy: Illumina; Honoraria (self), Advisory / Consultancy: InteRNA Technologies; Full / Part-time employment, Officer / Board of Directors: Hartwig Medical Foundation. H.M.W. Verheul: Honoraria (institution), Advisory / Consultancy: Glycostem; Honoraria (institution), Advisory / Consultancy: Lava Therapeutics. H. Gelderblom: Research grant / Funding (institution): Five Prime; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Debio; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Teva. All other authors have declared no conflicts of interest.

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Proffered Paper session: Genomic characterization of cancer cells to guide precision medicine: Next steps Proffered Paper session

Invited Discussant LBA26 and LBA27 (ID 7255)

Lecture Time
15:35 - 15:50
Speakers
  • Ruth Plummer (Newcastle upon Tyne, Tyne and Wear, United Kingdom)
Location
Salamanca Auditorium (Hall 3), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
15:00 - 16:05
Proffered Paper session: Genomic characterization of cancer cells to guide precision medicine: Next steps Proffered Paper session

Ranking genomic alterations for precision medicine: New developments of ESCAT (ID 7289)

Lecture Time
15:50 - 16:05
Speakers
  • Joaquin Mateo (Barcelona, Spain)
Location
Salamanca Auditorium (Hall 3), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
15:00 - 16:05