Abstract 10P
Background
Appendix cancers (AC) are rare, with frequent peritoneal metastasis (PM). Limited chemotherapy options are extrapolated from colorectal cancer. The aim was to evaluate outcomes of AC by molecular subgroup to understand chemotherapy outcome and new opportunities for treatment.
Methods
We collected clinically indicated next generation sequencing (NGS) data from PM or primary tumour specimens from a prospective database of patients with AC. Testing was done on FFPE tissue (<=37 genes) or on fresh blood (>300 genes). Primary outcome was overall survival (OS).
Results
There were 55 AC patients with molecular data between 2005-2022: Adenocarcinoma types: 21 mucinous (MAC), 8 not otherwise specified (ANOS), 25 goblet cell (GCA) and 1 signet ring cell (SRC). Median age was 55 (31-75) and 51% were male. There were 47 (85%) with PM. Median peritoneal cancer index (PCI) was 11 (0-39). There were 42 (76%) who had cytoreductive surgery; 26/42 (62%) had no or <0.25cm residual disease. There were 48 (87%) who had chemotherapy; 10 (9 GCA) received anti-EGFR antibody (antiEGFR). Neoplastic cell content was reported in 18 samples; 8 were <20% (included) and 2 were insufficient (excluded). Of 53 remaining, 27 (55%) had a KRAS mutation (KRASm) of which 12 (24%) were G12D. Median mutant allele frequency was 10% (2-33%). NGS >300 gene panel was done on 6 (12%) patients. Other mutations included 3 TP53, 2 NRAS, 2 GNAS, 1 PI3KCA and 1 BRCA2. After median follow-up 51 months (m), KRASm patients had similar survival to those irrespective of histology or chemotherapy receipt (Table). Patients without KRASm who had chemotherapy and antiEGFR had shorter OS compared to chemotherapy alone (median NR vs 20m, 95% CI 7-34, p=0.015; Table). Table: 10P
| Overall survival | Median (95% CI), m | ||
| KRASm | KRAS WT | p | |
| All | 82 (2-162) | 43 (24-63) | 0.55 |
| MAC | 29 | 27 (20-34) | 0.63 |
| ANOS | 82 | 46 (0-99) | 0.65 |
| GCA | 36 (18-53) | 49 (31-67) | 0.97 |
| Chemotherapy | |||
| No | 90 | 49 | 1.0 |
| Yes | 82 (9-155) | 41 (22-61) | 0.48 |
| + AntiEGFR | |||
| No | NR | 0.015 | |
| Yes | 20 (7-34) |
Conclusions
KRASm are common in AC, the most frequent in our series being G12D at 24%, with implications for access to trials of pan and KRASG12C inhibitors. AntiEGFR was associated with a worse prognosis in our series of mostly GCA. A challenge for molecular testing includes lower neoplastic cell content due to diffuse PM.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The Christie NHS Foundation Trust.
Funding
Has not received any funding.
Disclosure
M.C. Strach: Financial Interests, Personal, Advisory Board: Specialised Therapeutics; Financial Interests, Personal, Other, Fellowship: ESMO; Financial Interests, Institutional, Research Grant: Royal Prince Alfred Hospital; Financial Interests, Personal, Funding, Travel Fellowship: Royal Australasian College of Physicians; Financial Interests, Personal, Funding, PhD Scholarship: Australian Government Research Training Scholarship; Financial Interests, Institutional, Funding: Christie Charitable Funds. S. O'Dwyer, O. Aziz: Financial Interests, Institutional, Research Grant: Cancer Research UK; Financial Interests, Personal, Member, Academy: R&D. J. Barriuso: Financial Interests, Personal, Invited Speaker: Pfizer, Ipsen, NanoString, Servier; Financial Interests, Personal, Advisory Board: Nutricia; Financial Interests, Personal, Expert Testimony: AAA; Non-Financial Interests, Personal, Project Lead: EORTC; Non-Financial Interests, Personal, Invited Speaker: GETNE; Non-Financial Interests, Personal, Principal Investigator: ENETS. All other authors have declared no conflicts of interest.