Hyperprogressive disease in early-phase immunotherapy trials: clinical predictors and association with immune-related toxicities


A subset of patients treated with immune checkpoint inhibitors experience an accelerated tumor growth rate ( TGR ) in comparison with pretreatment kinetics; this is known as hyperprogression.
A study has assessed the relation between hyperprogressive disease ( HPD ) and treatment-related toxicity and clinical factors.

The study reviewed patients with solid tumors who were enrolled in early-phase immunotherapy trials at Princess Margaret Cancer Centre ( Toronto, Ontario, Canada ) between August 2012 and September 2016 and had computed tomography scans in the pre-immunotherapy ( reference ) and on-immunotherapy ( experimental ) periods.

Hyperprogression was defined as progression according to Response Evaluation Criteria in Solid Tumors ( RECIST ) 1.1 at the first on-treatment scan and a greater than or equal to 2-fold increase in tumor growth rate between the reference and experimental periods.
Treatment-related toxicities requiring systemic therapy, drug delays, or discontinuation were considered clinically significant adverse events ( CSAEs ).

Of 352 patients, 182 were eligible for analysis. The median age was 60 years, and 54% were male. The Eastern Cooperative Oncology Group ( ECOG ) performance status was 0 ( 32% ) or 1 ( 68% ).
The Royal Marsden Hospital ( RMH ) prognostic score was 0/1 in 59%.
Single-agent immunotherapy was given to 80% of the patients.
Most patients ( 89% ) received anti-programmed death ( ligand ) 1 antibodies alone or in combination with other therapies.

Hyperprogression occurred in 12 of 182 patients ( 7% ).

A higher proportion of females was seen among HPD patients ( P = 0.01 ), but no association with age, performance status, tumor type, RMH prognostic score, combination immunotherapy, or CSAEs was found.

The 1-year overall survival rate was 28% for HPD patients and 53% for non-HPD patients ( hazard ratio, HR=1.7; 95% confidence interval, 0.9-3.3; P = 0.11 ).

In conclusion, hyperprogression was observed in 7% of patients with solid tumors treated with immunotherapy.
Hyperprogression was not associated with clinically significant adverse events, age, tumor type, or the type of immunotherapy but was more common in females. ( Xagena )

Kanjanapan Y et al, Cancer 2019;125:1341-1349

XagenaMedicine_2019



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