1572 - Impact of Immunotherapy and Targeted Therapy on Tumor Growth Rate in Sarcoma

Background

With increasing use of immunotherapy and targeted treatments in oncology, it is essential to understand the biological effects of these therapies on tumor kinetics. This retrospective review aims to identify hyperprogressive disease (HPD) occurrence in sarcoma patients treated with immunotherapy or targeted therapy, and its effect on overall survival.

Methods

We performed a retrospective review of advanced sarcoma patients enrolled in immunotherapy or targeted therapy clinical trials at the Princess Margaret Cancer Centre, Toronto. Tumor growth rate (TGR) was assessed for each patient based on serial CT scans at pre-baseline, baseline and on-treatment timepoints. TGR was calculated using a published formula (Champiat et al. 2017), and the ratio between reference and experimental groups was then calculated. The predictive accuracy of HPD was assessed using Cox proportional hazards analysis both as a continuous variable and using a cut-off for TGR ratio percentage of more than 50%. Statistical significance was defined as p < 0.05.

Results

We identified 146 patients who were treated with immunotherapy, targeted therapy, or combination chemotherapy and targeted therapy between July 26, 2013, and August 7, 2018. 106 patients met the eligibility criteria. 20 patients received immunotherapy, 86 patients received targeted or combination chemotherapy and targeted therapy. Three patients from the immunotherapy group had HPD (15%), and two patients from the non-immunotherapy group had HPD (2.3%). The hazard ratio for the patients with TGR ratio percentage of ≥ 50%(HPD) was 9.34 (95% CI 3.38-25.84, p = < 0.001). The median survival in all patients with HPD vs non-HPD was 3.9 months (95% CI 2.5-5.2 months) vs 16.1 months (95 % CI 13-19.2 months). There was no interaction between HPD and receipt of immunotherapy vs other therapy.

Conclusions

There is a correlation between TGR and clinical outcomes in patients with sarcoma treated with immunotherapy or targeted therapy. HPD is associated with worse survival outcomes and may serve as a useful tool in the assessment of treatment futility during patient therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Abdul Razak Ryan Albiruni.

Funding

Has not received any funding.

Disclosure

E. Amir: Speaker Bureau / Expert testimony: Genentech/Roche; Honoraria (self): Apobiologix ; Advisory / Consultancy: Agendia; Advisory / Consultancy: Myriad Genetics. A.R.R. Albiruni: Honoraria (self): Boehringer Ingelheim ; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (self): CASI Pharmaceuticals; Research grant / Funding (self): Lilly; Research grant / Funding (self): Novartis; Research grant / Funding (self): Deciphera; Research grant / Funding (self): Karyopharm Therapeutics; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Roche/Genentech; Research grant / Funding (self): Boston Biomedical; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): MedImmune; Research grant / Funding (self): Amgen; Research grant / Funding (self): GlaxoSmithKline; Research grant / Funding (self): Blueprint Medicines; Research grant / Funding (self): Merck; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Adaptimmune. All other authors have declared no conflicts of interest.