Abstract 4771
Background
Metastatic non-colorectal cancers have adverse prognosis and no target or immunotherapy is approved until now. NGS platforms are supposed to be useful tailoring systemic treatments and/or screening patients(pts) for early phase clinical trials. Although attractive, NGS-tailored therapies (NGS-TT) can have disappointing results in not approved indications outside clinical trials. In this analysis we evaluated the tumor genetic profiles including potential germline mutations, suggested therapies, available clinical trials, and the results for off-label NGS-TT.
Methods
we performed a retrospective assessment of clinical and molecular characteristics, NGS-TT prescribed and responses in a cohort of MNCGIC evaluated through the 315 genes NGS platform between 2013-2019. We looked for potential germline mutations in mismatch-repair genes and BRCA1/2, as well as the TP53R337H founder mutation.
Results
among 78 pts, the median age was 58.5y (20-79), with 51 (65%) males and 27 (35%) females. The most common sites were pancreas (41%), stomach (15.4%) and biliary tract (15,4%); 83% were ECOG 0/1, with up to 2 lines of therapy (60.25%). Mean number of altered genes was 4.41 (1-19) and tumor mutational burden (TMB) was assessed in 24 pts, with 79% TMB-low (mean 5.22 muts/Mb). Ten pts (12.85%) underwent off-label NGS-TT after discussion at multidisciplinary tumor boards; among 9 available for response evaluation, 7 experienced progression as best response. Clinical trials were suggested for 73 pts (93,6%), but only one patient (pt) was referred to it, since all trials where abroad. We also identified 3 cases for which germline sequencing would be of value (1 pt with TP53 R337H mutation; 2 young gastric cancer pts: one with concurrent MSH6/BRCA2 mutations and another with MLH1truncation exon10 alteration).
Conclusions
in our cohort, the adoption of NGS to tailor systemic treatment did not show an important impact for MNCGIC pts. Increase participation of developing country centers in clinical trials is strongly needed. Potentially germline mutations were present in this series and deserve further investigation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
D. de Freitas: Honoraria (self): Roche. D.L.F. Jardim: Honoraria (self): Foundation Medicine. B. Gumz: Honoraria (self): Novartis. All other authors have declared no conflicts of interest.
Resources from the same session
5650 - Tissue-based activation of mucosal-associated invariant T (MAIT) cells in combination ipilimumab and nivolumab checkpoint inhibitor (CI) colitis.
Presenter: Sarah Sasson
Session: Poster Display session 3
Resources:
Abstract
5944 - Significance of severe immune-related adverse effects (irAE) on patients with advanced tumors treated with immune checkpoint inhibitors being admitted for secondary toxicity: Clinical relevance and next steps
Presenter: Leyre Zubiri
Session: Poster Display session 3
Resources:
Abstract
5989 - Implementation of a dedicated immuno-oncology toxicity service reduces the acute impact of immune-related adverse events
Presenter: Anna Olsson-Brown
Session: Poster Display session 3
Resources:
Abstract
3267 - Cardiotoxic and pro-inflammatory effects induced by the association of immune checkpoint inhibitor Pembrolizumab and Trastuzumab in preclinical models
Presenter: Nicola Maurea
Session: Poster Display session 3
Resources:
Abstract
3417 - Interstitial lung disease associated with immune-checkpoint inhibitors in malignant diseases
Presenter: Akira Yamagata
Session: Poster Display session 3
Resources:
Abstract
2071 - A Phase 1 Study of Intraperitoneal MCY-M11 Anti-Mesothelin CAR for Women with Platinum Resistant High Grade Serous Adenocarcinoma of the Ovary, Primary Peritoneum, or Fallopian Tube, or Subjects with Peritoneal Mesothelioma with Recurrence after Prior Chemotherapy
Presenter: Christina Annunziata
Session: Poster Display session 3
Resources:
Abstract
4935 - Trial in progress: First-in-human study of a novel anti-NY-ESO-1–anti-CD3, TCR-based bispecific (IMCnyeso) as monotherapy in NY-ESO-1/LAGE-1A-positive advanced solid tumors (IMCnyeso-101)
Presenter: Juanita Lopez
Session: Poster Display session 3
Resources:
Abstract
5613 - Nimotuzumab-Cisplatin-Radiation versus Cisplatin-Radiation in HPV negative oropharyngeal cancer
Presenter: Kumar Prabhash
Session: Poster Display session 3
Resources:
Abstract
2576 - Interim analysis of a single arm phase 2 study of adjuvant nivolumab after salvage resection in head and neck squamous cell carcinoma patients previously treated with definitive therapy.
Presenter: Trisha Wise-draper
Session: Poster Display session 3
Resources:
Abstract
4758 - A Phase I Study of the CDK4/6 Inhibitor, Palbociclib in combination with Cetuximab and Intensity Modulated Radiation Therapy (IMRT) for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN); A Result of Dose Escalation Cohort
Presenter: Nuttapong Ngamphaiboon
Session: Poster Display session 3
Resources:
Abstract