ESMO Congress 2023 | OncologyPRO

Abstract 138P

Background

The improved understanding of the biological mechanisms of the homologous recombination repair and the emergence of PARP inhibitors has opened new therapeutic options for patients with progressive cancers on standard treatments. The MOST study was designed to treat patients with metastatic solid tumors according to specific molecular alterations. We present here the results of the olaparib cohort.

Methods

The MOST trial is an ongoing multicenter, prospective, randomized study conducted in six French university hospitals. Patients known to have germline or somatic alterations in the homologous recombination genes received olaparib (300mg, BID) outside standard recommendations, until disease progression, unacceptable toxicity, patient's or investigator's decision. Disease response was evaluated at 12 weeks of treatment per RECIST criteria.

Results

Amongst the 213 included patients (63.4% female, median age: 58 years [26- 85], median number of prior lines of treatment: 3 [1-16]) e.g. platinium 63%), the main initial tumor sites were breast (25.8%), pancreas (19.2%), colorectal (7.5%), sarcoma (6.1%) and brain (5.2%). Tumor response after 12 weeks (W12) according to main HRD genes altered (>5%) are presented in table. Patients with PALB2 mutations showed the best disease control rate. Grade 3 or higher adverse events were reported in 81 patients (38%). Table: 138P

Tumor status at week 12 for the main molecular alterations (>5%)

Tumor status	CR or PR	SD	PD	Treatment discontinuation
All patients (n=213)	n=14 (6%)	n =34 (16%)	n=161 (76%)	n=4 (2%)
Gene altered, N (% of population)
BRCA1, N = 26 (12.2%)	0 (0.0%)	3 (11.5%)	23 (88.5%)	0 (0.0%)
BRCA2 N= 49 (23%)	8 (16.3%)	5 (10.2%)	36 (73.5%)	0 (0.0%)
PALB2 N= 15 (7%)	4 (26.6%)	2 (13.3%)	8 (53.3%)	1 (6.6%)
ATM N= 49 (23%)	1 (2%)	11 (22.4%)	37 (75.5%)	0 (0.0%)
BAP1 N= 14 (6.6%)	1 (7.1%)	3 (21.4%)	10 (71.4%)	0 (0.0%)

CR/PR/SD/PD according to RECIST. Treatment discontinuation before W12 was due to toxicity or patient decision.

Conclusions

Overall, only a minority of patients benefit from olaparib treatment after 12 weeks of treatment even though their tumor harbor HRD gene alterations, with a 3-month PFS rate of 23% (48/213). Translational research is ongoing to explore which genomic signature is associated with olaparib response.