1084 - Dissociated responses in patients with metastatic solid tumors treated with immunotherapy

Background

Immune checkpoint inhibitors (ICI) have been demonstrated to improve overall survival (OS) in several cancer types. Atypical patterns of response have been reported including durable responses, pseudoprogression and hyperprogression. We evaluated the occurrence of dissociated response (DR) on immunotherapy.

Methods

We retrieved all patients treated at the Curie Institute with an ICI either alone or in combination with another ICI in the frame of a clinical trial. Patients had to have a baseline CT-scan and at least one follow-up CT-scan, and at least two target lesions (TLs). There was no selection on tumor type. All TLs on CT-scans were assessed by two independent readers according to RECIST 1.1. Three types of DR were evaluated: 1) one TL in partial or complete response (CR/PR) and one progressive TL (DR1), 2) one stable TL and one progressive TL (DR2), and 3) one TL in CR/PR and one stable TL (DR3). Finally, we evaluated the impact of previous radiotherapy and biopsy on TLs on the occurrence of DRs.

Results

1,246 measures of 272 TLs were performed in the 100 patients who met our inclusion criteria. The median number of TLs per patient was 3 [range: 2-5]. 49 out of the 272 TLs (18%) had received prior radiotherapy, and 38 (14%) had been biopsied. Median progression-free survival (PFS) was 3.8 months. Median OS was 13.4 months. Best overall response per patient was a PR/CR in 22%, stable disease (SD) in 33% and progressive disease (PD) in 45%. Best overall response on 272 TLs was a PR/CR in 52 TLs (19%), SD in 142 TLs (52%) and PD in 78 TLs (29%). DR1 were observed in 8% of patients, whereas DR2 and DR3 were observed in 44% and 10% of patients, respectively. While prior irradiation on TLs did not correlate with the occurrence of DRs, DRs were more common when one TL was biopsied ORa = 2.22 (1.28, 3.86) (p = 0.004).

Conclusions

DR with a responding TL and a progressive TL according to RECIST1.1 was observed in 8% of patients. While prior irradiation on TLs did not correlate with the occurrence of DRs, DRs were more common when one TL was biopsied.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

D. Loirat: Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Novartis; Honoraria (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Pfizer. C. Le Tourneau: Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Amgen; Advisory / Consultancy: Merck; Advisory / Consultancy: Serono; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Nanobiotix; Advisory / Consultancy: GSK. All other authors have declared no conflicts of interest.