Abstract 4727
Background
Limited data exist in the clonal dynamics of serial ctDNA as a predictive biomarker in advanced solid tumor pts receiving immune checkpoint blockade.
Methods
Pts with mixed solid tumors received single agent P (anti-PD-1) 200 mg IV Q3wks in the investigator-initiated phase II INSPIRE trial (NCT02644369). ctDNA was assayed at baseline (B) and start of cycle 3 (C3) using a pt-specific amplicon-based NGS assay (Signatera™). Samples were considered ctDNA positive if ≥ 2 of 16 pt-specific targets met the qualifying confidence score threshold.
Results
Of 94 pts are presented. Demographics: male 38%; median age=55 yrs (range 21–81); triple negative breast (19%), ovarian (19%) and head and neck (17%) cancers comprised the major malignancies. Median no. of P cycles=3 (range 1–35); follow up was 14m (range 0.6-35.4); RECIST responses: CR 3.2% (n = 3), PR 14% (n = 13), CBR (CR+PR+SD>6 cycles) 28% (n = 26), RECIST/clinical PD (n = 61/18; 65%/19%). Median PFS=2.5m and median OS = 14m. In all 94 pts, ctDNAB correlated with PFS (adjusted HR 0.53, 95% CI 0.34-0.84, p = 0.01) and OS (adjusted HR 0.47, 95% CI 0.28-0.8, p = 0.01). Among 74 pts with both ctDNAB and ctDNAC3, the change (ΔctDNA) correlated with clinical efficacy parameters (Table).Table: 113P
Endpoint | ORR N = 72* | CBR N = 72* | Endpoint | PFS N = 73* | OS N = 73* | ||||
---|---|---|---|---|---|---|---|---|---|
Subgroup | CR/PR N = 15 | SD/PD N = 57 | CR/PR/SD≥6 cycles N = 22 | CR/PR/SD<6 cycles N = 50 | Subgroup | ↑ from baseline N = 33 | ↓ from baseline N = 40 | ↑ from baseline N = 33 | ↓ from baseline N = 40 |
ΔctDNA (% change) | Median = -91.5% Range = -100% to 60% | Median = 40% Range = -98.4% to 2458% | Median = -75% Range = -100% to 96% | Median = 52% Range = -94.6% to 2458% | Results based on ΔctDNA | Median = 7.9m 6m = 51.5% | Median = 2.8m 6m = 10.0% | Median = not reached 6m = 91% 12m = 82% | Median = 9.1m 6m = 73% 12m = 45% |
P-value | P < 0.001 | P < 0.001 | Adjusted HR (95% CI)^ | 0.43 (0.25-0.75) P = 0.003 | 0.35 (0.18–0.67) P = 0.002 |
Adjustment on cohorts;
*2 pts were excluded from ORR/CBR analyses as baseline ctDNA = 0; 1 of these 2 pts (with PR) excluded from PFS/OS analyses as C3 ctDNA = 0
Conclusions
Strong correlations exist between both ctDNAB and ΔctDNA with clinical outcome, suggesting both prognostic and predictive values in pts with mixed solid tumors.
Clinical trial identification
NCT02644369, December 31, 2015.
Editorial acknowledgement
Legal entity responsible for the study
University Health Network, Toronto.
Funding
Merck, Netera, Terry Fox Research Institute, Princess Margaret Cancer Foundation.
Disclosure
S. Dashner: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netera. A.R. Hansen: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Boehringer-Ingelheim; Research grant / Funding (institution): AstraZeneca/Medimmune; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Karyopharm. P. Bedard: Honoraria (institution), Advisory / Consultancy: Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): AstraZeneca/Medimmune; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Nektar Therapeutics; Research grant / Funding (institution): Servier; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): PTC Therapeutics; Research grant / Funding (institution): Oncothyreon. S. Lheureux: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca/Medimmune; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Tesaro. A. Spreafico: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Oncorus; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): AstraZeneca/Medimmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Surface Oncology; Research grant / Funding (institution): Northern Biologics; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Oncology/Johnson & Johnson; Research grant / Funding (institution): Array Biopharma. A.A. Razak: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): CASI Pharmaceuticals; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Karyopharm Therapeutics; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): AstraZeneca/Medimmune; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Adaptimmune. H. Wu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netera. S. Shchegrova: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netera. P.S. Ohashi: Honoraria (self), Advisory / Consultancy: Symphogen Inc; Honoraria (self), Advisory / Consultancy: Providence Therapeutics. M. Louie: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netera. H. Sethi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netera. A. Aleshin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netera. L.L. Siu: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfiser; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca/Medimmune; Honoraria (self), Advisory / Consultancy: Morphosys; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Honoraria (self), Advisory / Consultancy: GeneSeeq; Honoraria (self), Advisory / Consultancy: Loxo; Honoraria (self), Advisory / Consultancy: Oncorus; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Symphogen; Honoraria (self), Advisory / Consultancy: Seattle Genetics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Boerhinger-Ingelheim; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Intensity Therapeutics; Research grant / Funding (institution): Mirati; Research grant / Funding (institution): Shattucks; Spouse / Financial dependant: Agios. S. Bratman: Research grant / Funding (self): Nektar Therapeutics; Licensing / Royalties, Co-inventor of a patent relating to circulating tumor DNA detection technology: Roche Molecular Diagnostics. T.J. Pugh: Honoraria (self): Merck; Honoraria (self): Prosigna; Honoraria (self): Chrysalis Medical Advisors; Advisory / Consultancy: DynaCare; Research grant / Funding (self): Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Resources from the same session
3361 - Providing a nurse-led telephone intervention for patients treated with oral anticancer medication: symptom management and adherence monitoring
Presenter: Etienne Minvielle
Session: Poster Display session 3
Resources:
Abstract
3937 - Chronological evaluation of health-related quality of life and physical symptoms in postoperative pancreatic cancer patients up to 12 months
Presenter: Naoko Sato
Session: Poster Display session 3
Resources:
Abstract
5620 - Understanding the patients’ Experiences of Radiation Therapy: A Qualitative Study on Prostate Cancer Patients
Presenter: Sakarias Johansson
Session: Poster Display session 3
Resources:
Abstract
1792 - Effect of Kegel exercises on prevention of urinary and fecal incontinence in patients with prostate cancer undergoing radiotherapy
Presenter: Aydan Uravylioglu
Session: Poster Display session 3
Resources:
Abstract
2169 - The Meaning of Responsibility – a Secondary Analysis of Patients and Caregivers Calls to an Oncology Emergency Telephone
Presenter: Heidi Jacobsen
Session: Poster Display session 3
Resources:
Abstract
4587 - Cognitive function changes and Associated Factors in Patients Receiving Chemotherapy
Presenter: Elif Dil
Session: Poster Display session 3
Resources:
Abstract
1981 - Prevention of dental complications in patients with multiple myeloma (MM) receiving bisphosphonates treatment
Presenter: CESCA PUIGMARTI
Session: Poster Display session 3
Resources:
Abstract
2725 - Safety profile of oral netupitant/palonosetron in hematopoietic stem cell transplantation recipients.
Presenter: Marina Bosch - Damas
Session: Poster Display session 3
Resources:
Abstract
5112 - Symptomatic and toxicity management of cancer patients using a telephone support model led by the oncology nurse
Presenter: Gemma Simó
Session: Poster Display session 3
Resources:
Abstract
1365 - Symptom cluster of fatigue, sleep disturbance and depression and its impact on quality of life among Chinese breast cancer patients undergoing adjuvant chemotherapy: A cross-sectional study
Presenter: Xiaole HE
Session: Poster Display session 3
Resources:
Abstract