Abstract 1522P
Background
The use of novel antiangiogenic TKIs (AA-TKIs) has emerged as a major paradigm shift in recurrent sarcoma. Previous trials demonstrated an ORR of 8 ∼ 22% as monotherapy, and an ORR of 24∼29% as combination therapy against advanced sarcoma. However, it is still unknown whether a drug holiday of AA-TKIs is safe and feasible in patients with favorable response.
Methods
We aim to retrospectively explore the outcome of AA-TKI holiday in advanced sarcoma showing a (near-)complete remission or long-term (>6 months) response. Given that sarcoma with solitary, late metastasis may be cured without systemic therapy, we only included patients unlikely to be cured at the initiation of AA-TKI having ≥1 risk factors: Bilateral lung metastasis; Metastasis plus local or extrapulmonary lesions; Disease-free interval (DFI) <18 months; Inoperable; > 5 metastases).
Results
A total of 22 patients with apatinib (n=14), anlotinib (n=6) and pazopanib (n=2) discontinuation after favorable response were analyzed, with median follow-up of 35.5 mo. At the time of discontinuation, there were 12 surgical CR (due to downstaging), 4 drug-induced CR and 6 long-term stable disease. Post-discontinuation disease progression(pd-PFS) after discontinuation was observed in 17 of 22 patients (77.3%), with a median interval of 6.5 mo. However, since the majority were still sensitive to the original AA-TKIs (ORR 50% and DCR 71.43% upon re-administration) or amenable to second surgical remission, 7 of 17 patients achieved a second CR after disease progression and thus considered as still relapse-free post-discontinuation (pd-RFS). Therefore, the pd-RFS and pd-OS at the last follow-up were 12/22 (54.5%) and 16/22 (72.7%), respectively. Remarkably, we found that surgical CR (compared to drug only) and drug tapper-off (compared to abrupt withdrawal) was associated with greater pd-RFS and pd-OS (p<0.05). Furthermore neutrophil-to-lymphocyte ratio (NLR) greater than the 2.5 before discontinuation (p=0.055) was also predictive of worse pd-RFS.
Conclusions
AA-TKI discontinuation with taper-off strategy might be feasible in highly selected patients. Surgical CR and lower NLR were potential candidate biomarker for AA-TKIs withdrawal.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Ruijin hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.