100P - Biomarkers of immune therapy in CUP

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer in Adolescents
Carcinoma of Unknown Primary Site
Translational Research
Presenter Joanne Xiu
Citation Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363
Authors J. Xiu1, Z. Gatalica2
  • 1Medical Affairs, Caris Life Sciences, 85040 - Phoenix/US
  • 2Pathology, Caris Life Sciences, 85040 - phoenix/US

Abstract

Background

Carcinoma of unknown primary (CUP) accounts for approximately 3% of all malignancies. Identification of common cancer pathway alterations (hallmarks of cancer) in diverse cancer lineages offers a rationale for search for biomarkers of targeted therapies in patients with CUP. Avoiding immune destruction is a more recently recognized common cancer characteristic and biomarkers associated with immune check-point blockade were explored in this study.

Methods

392 cases of CUP were tested with NextSeq platform with a 592-gene panel. Tumor mutational load (TML) was calculated using only somatic nonsynonymous missense mutations; microsatellite instability (MSI) was evaluated with NGS by direct analysis of known MSI loci in the target regions of the sequenced genes. ArcherDx FusionPlex Assay was used to detect gene fusions and 52 gene targets were analyzed for 156 tumors. IHC was used to detect tumor expression of PD-L1 (SP142 antibody) and PD-1 TILs (NAT105 antibody) All tests were done in a CLIA-certified lab.

Results

Average patient’s age was 62.4 years; 52% were female. TML high was seen in 12.2% (48/392) tumors using a cutoff of 17 mutations/Mb. MSI-high was detected in 10/392 (2.6%) of tumors. A total of 70 different genes were found mutated with the incidence ranging from 0.3% to 54%; the most frequent were TP53 (53.5%), KRAS (21.5%) and ARID1A (14.6%). Additional notable targetable mutations include PIK3CA (13.1%), CDKN2A (8.1%), PTEN (4.5%), BRAF (4.1%), ATM (3.3%), NOTCH1 (2.4%) and ERBB2 (1.5%). Targetable gene fusions identified included FGFR2 fusions (N = 2), RET (N = 1), RAF1 (N = 1).Tumors with fusions identified carry a lower TML (average 5.9) than the complete cohort (11.7, p 

Conclusions

Using a multiplex testing approach, 28% of CUPs had biomarkers (TML-H, MSI-H and/or PD-L1) of response to the immune check-point blockade were identified, making CUP one of the most likely candidate to benefit from immune checkpoint inhibitors.

Clinical trial identification

Legal entity responsible for the study

Joanne Xiu

Funding

None

Disclosure

J. Xiu, Z. Gatalica: Employee of Caris Life Sciences.