Abstract 1656P
Background
AIP in sarcoma has been widely noticed as a hard to treat complication, leading to dismal outcomes. Although drug interruption is usually indicated, anecdotal evidence has identified some AIP patients continuing anti-angiogenic therapy (AAT) during AIP as exceptionally durable responders.
Methods
A total of 131 sarcoma pts were treated with apatinib-containing therapy in our institution. From Sep. 2017, we implemented a non-stop strategy for 28 sarcoma pts with AIP using a multi-disciplinary approach to avoid interrupting AAT. Another 10 AIP pts treated with drug interruption strategy (pts decision or referral from other institution) served as a pragmatic control.
Results
AIPs were significantly enriched in young, heavily pre-treated, male patients with lung metastases with cavitary changes. AIPs with non-stop strategy were associated with drastically longer progression-free survival (PFS) (12.0 mo), compared to those without AIP (6 mo) or AIP with drug interruption (4.0 mo) (P=0.003), with the best even >3 yr. Such benefit was further translated into pts' overall survival, with a borderline statistical significance (AIP group 23.3 mo vs control 16.9 mo, P=0.099). There were no deaths directly related to the pneumothorax. Removal of chest tube was achieved in 31 (81%) of the pts, while 4 lived with permanent tubing and 3 died from complications of long-term tubing. Interestingly, cavitary lesions presented in all ages (rather than only in young pts) and the concurrence of AIP and cavitation accounted for only 54% of the cases, suggesting additional contributing factors of AIPs. To this end, 21 common SNPs were screened, and VEGFR2 A-to-G polymorphism (rs2071559) remained as the only biomarker for both the therapeutic efficacy and the risk of AIPs. RNA-seq data of 21 osteosarcomas suggest a different phenotype of the vasculature between the AA versus the A-to-G genotype. To test the generalizability of our result, we reviewed 31 previously published trials and found that there is a general correlation of the AIP incidence with the treatment efficacy, in terms of overall response rate (ORR) (r=0.64, P<0.001) and PFS (r=0.44,P=0.014), further supporting that AIP might be an efficacy related AE deserving attentions.
Conclusions
Our multidisciplinary strategies assure sarcoma pts with AIP to remarkably benefit from AAT as durable responders. Further investigation of the germline biomarker of AIP for risk stratification and individualized regimens is warranted.
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.