Abstract 120P
Background
Hyperprogressive disease (HPD) is an atypical response to immune checkpoint inhibitors (ICIs) therapy. The definition of HPD is not yet clearly established, and it is unclear which patient is rapidly progressing after immunotherapy (IMT). Identification of predictive biomarkers for atypical responses either before or during treatment remains a huge unmet need in cancer IMT.
Methods
Medical records from all patients treated in our hospital by ICIs were analyzed. Data were obtained of our electronic medical record and molecular database. HPD was defined as a RECIST progression at the first evaluation and as a ≥2-fold increase of the TGR between the “reference” and the “experimental” periods. Next Generation Sequencing (NGS) was performed on pre-treatment tumor tissue or trough analysis of cfDNA circulating in blood (liquid biopsy).
Results
6 patients met criteria for HPD, NGS data was available on 2 patients and liquid biopsy on 3 patients. Most frequently encountered somatic alterations (SA) were TP53 and STK11. Two patients with HPD had a stable Microsatellite Instability status (MSI) and a Tumor Mutational Burden (TMB) of 0 and 9 Muts/MB respectively; however, other 2 patients had an undetermined MSI and TMB. Table: 120P
Patient characteristics
| Age | Sex | Cancer disease | Clinical stage | # Prior lines of chemotherapy | ICI | Time to HP (months) | TMB (Muts/MB) | MSI | NGS | Liquid biopsy |
| 60 | M | Lung | IV | 2 | Pembrolizumab | 3 | 9 | Stable | TP53, WT1, ATM, APC, ARHGEF12, CDK12, CLTCL1, EP300, HSP90AA1, IGF1R, INHBA, LRP1B, MECOM, MUTYH, NTRK2, PER1, WRN, ZNF521 | TP53, CCNE1, KIT |
| 42 | F | Breast | IV | 1 | Atezolizumab | 3 | 0 | Stable | STK11, TP53, RB1, SPEN, EP300, FGFR3, LTK, SOCS1, TSC1, TSC2 | NA |
| 56 | M | Lung | IV | 1 | Pembrolizumab | 3 | - | Undetermined | NA | RET, ATM, STK11, CHEK2, NF1 |
| 50 | M | Kidney | IV | 1 | Nivolumab + Ipilimumab | 3 | - | Undetermined | NA | GNAS, TP53, EGFR |
| 46 | M | Kidney | IV | 1 | Nivolumab | 3 | NA | NA | NA | NA |
| 45 | F | Breast | IV | 2 | Atezolizumab | 3 | NA | NA | NA | NA |
Conclusions
A subset of patients treated with ICIs developed HPD (6.97%) and we found some of the SA reported in previous studies (STK11, TP53). The role of SA as putative biomarkers of HPD requires further validation in larger cohorts with the goal of prospectively identifying patients at risk of developing HPD trough genomic profiles.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.