Financial support: European Union's Seventh Program for research, technological development and demonstration (agreement N°304810), the Fondation ARC pour la recherche contre le cancer.

Precision oncology is currently based on pairing molecularly targeted agents (MTA) to predefined single driver genes or biomarkers. Each tumor harbors a combination of a large number of potential genetic alterations of multiple driver genes in a complex system that limits the potential of this approach. We have developed an artificial intelligence (AI)-assisted computational method, the digital drug-assignment (DDA) system, to prioritize potential MTAs for each cancer patient based on the complex individual molecular profile of their tumor. We analyzed the clinical benefit of the DDA system on the molecular and clinical outcome data of patients treated in the SHIVA01 precision oncology clinical trial with MTAs matched to individual genetic alterations or biomarkers of their tumor. We found that the DDA score assigned to MTAs was significantly higher in patients experiencing disease control than in patients with progressive disease (1523 versus 580, P = 0.037). The median PFS was also significantly longer in patients receiving MTAs with high (1000+ <) than with low (<0) DDA scores (3.95 versus 1.95 months, P = 0.044). Our results indicate that AI-based systems, like DDA, are promising new tools for oncologists to improve the clinical benefit of precision oncology.

Background Immune checkpoint inhibitors have been demonstrated to improve overall survival. Atypical patterns of response have been reported, including dissociated response (DR). We evaluated the prevalence of DR. Patients and methods Patients had to have a baseline computed tomography (CT) scan and at least one follow-up CT scan and two target lesions (TLs). Three types of DR were evaluated using RECIST1.1: DR1, defined as at least one progressive and one responding TL; DR2, defined as at least one progressive and one stable TL; and DR3, defined as at least one stable and one responding TL. Results A total of 1244 measurements of 272 TLs were performed in 100 patients. Forty-nine out of the 272 TLs (18%) had received old or recent radiotherapy, and 42 (15%) had been biopsied. An objective response was observed in 22 patients (22%) and on 52 TLs (19%). DR1 were observed in 8% of patients. At the tumor measurement level, the response rate was lower in the case of prior radiotherapy (29% vs 34%, p = 0.01) and higher in the case of prior biopsy (40% vs 32%, p = 0.02). Conclusions A DR was observed in 8% of patients. Response rate was lower in the case of prior radiotherapy and higher in the case of prior biopsy.

BackgroundSOLAR-1 and BYLIEVE trials documented the e cacy of the PI3K-inhibitor alpelisib in pre-treated PIK3CAmutant, hormone receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer (ABC) patients.We report here real-life data of patients prospectively registered in the French alpelisib early access program (EAP). Patients and methods:The French EAP was opened to PIK3CA-mutant HR+/HER2-ABC patients treated with alpelisib and fulvestrant, managed per standard of care. Primary endpoint was PFS by local investigators using RECIST1.1. ResultsEleven centers provided individual data on 233 consecutive patients. Patients had received a median number of 4 (range: 1-16) prior systemic treatments for ABC, including CDK4/6 inhibitor, chemotherapy, fulvestrant and everolimus in 227 (97.4%), 180 (77.3%), 175 (75.1%) and 131 (56.2%) patients, respectively. After a median follow-up of 7.1 months and 168 events, median PFS was 5.3 months (95%CI, 4.7-6.0). Among 186 evaluable patients, CBR at 6 months was 45.3% (95%CI, 37.8-52.8). In multivariable analysis, characteristics signi cantly associated with a shorter PFS were age < 60 years (HR = 1.5, 95%CI = 1.1-2.1), > 5 lines of prior treatments (HR = 1.4, 95%CI = 1.0-2.0) and the C420R PI3KCA mutation (HR = 4.1, 95%CI = 1.3-13.6). Most frequent grade 3/4 adverse events (AEs) were hyperglycemia, rash, fatigue and diarrhea occurring in 11.6, 9.9, 4.3 and 3% of patients, respectively. N = 91 (39.1%) patients discontinued alpelisib due to AEs. DiscussionTo our knowledge, this is the largest real-life assessment of alpelisib e cacy. Despite heavy pretreatments, patients derived a clinically relevant bene t from alpelisib and fulvestrant. PFS was not overtly impaired by a prior use of either everolimus or fulvestrant. No new safety signal was found.

Background: Carboplatin-paclitaxel is standard of care for recurrent/advanced EC for which surgery AE radiation are not curative. Dostarlimab is an antieprogrammed cell death 1 (PD-1) humanized monoclonal antibody that showed antitumor activity and an acceptable safety profile in patients (pts) with recurrent or advanced EC in the GARNET trial. Niraparib is a PARP inhibitor (PARPi) approved as 1L maintenance therapy in pts with advanced ovarian cancer following response to platinum-based chemo. Based on mechanism of action and preclinical findings, PARPi are being investigated for use in EC. RUBY part 2 will evaluate the efficacy and safety of Annals of Oncology abstracts S770Volume 32 -Issue S5 -2021