85P - Stereotactic radiotherapy improves disease control in oligoprogressive patients included in early clinical trials

Background

Patients included in phase I trials are often heavily pre-treated and display strong treatment expectations. In some cases, oligoprogressive disease may occur but with pursued clinical benefit. In such scenarios, local ablative stereotactic radiotherapy (SRT) could allow disease control with prolonged use of current systemic treatment.

Methods

We retrospectively analysed data from patients included in early clinical trials who received SRT for oligo-acquired resistance (≤ 3 lesions of disease progression; OAR) between 01/2014 and 12/2021. OS, PFS1 (trial entry to OAR), PFS2 (SRT to subsequent relapse), time to next treatment (TTNT) were assessed. Subsequent patterns of relapse were distinguished as OAR2 or systemic AR (SAR).

Results

39 patients with 48 oligoprogressive lesions were included. Most frequent primary tumor histologies were NSCLC (33%), melanoma and urothelial carcinoma (13% each). Median age was 59 years, median baseline RMH score was 1 and 93% patients had an ECOG-PS<1. Early clinical trials mostly included ICI (64%) and molecular targeted therapies (MTT) (46%). SRT was mainly delivered to brain (38%) and lymph nodes (26%) at a median dose of 30 Gy. Median follow-up was 19 months. Median OS, PFS1, PFS2, and TTNT were respectively 16, 11, 7 and 9 months. PFS2 included 44% OAR2 and 56% SAR. No SRT-related grade 3-5 toxicity was observed. Increased OS was associated with primary tumor local control, higher baseline lymphocytes count, lower baseline RMH score, lower post-SRT tumor burden and absence of SAR. Increased TTNT was associated with primary tumor local control, absence of baseline polymetastatic disease, lower baseline RMH score, OAR2, OAR2-local treatment, and both lower baseline/post-SRT tumor burden. OAR2 was more often observed in MTT trials and SAR was associated with absence of primary tumor local control, short PFS1 and higher baseline tumor burden.

Conclusions

In pre-treated patients included in phase I trials, OAR managed with SRT led to durable benefit and prolonged continuation of investigational treatments. Predictive factors could be used for patient selection by distinguishing subsequent OAR2 from SAR.

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.