Novel NSCLC Hyperprogressive Disease Definition Proposed

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Researchers suggest an optimised definition for hyperprogressive disease (HPD) in advanced non-small-cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitor (ICI) therapy after analysing five of the existing definitions. 

“The findings of this retrospective cohort study of patients with NSCLC suggest that the previous 5 definitions of HPD were not associated with the same tumor behavior”, say Caroline Caramella, from Gustave Roussy and Université Paris-Saclay in Villejuif, France, and co-workers. 

“A new definition, based on ΔTGR [change in tumour growth rate] of greater than 100, appeared to be associated with the characteristics expected with HPD”, they say, namely an increase in both tumour kinetics and poor survival. 

The team applied HPD definitions to the medical records of 406 patients with stage III–IV NSCLC who received PD-1 or PD-L1 inhibitor therapy between 2012 and 2017 at one of eight French institutions. The patients all had at least two computed tomography scans taken before beginning ICI therapy and at least one during treatment after a median 62 days. 

The incidence of HPD varied depending on the definition used, the researchers note in JAMA Oncology.  

The rate was 5.4% when using a definition based on a twofold increase in pace of progression, at least a 50% increase in RECIST burden during treatment and a time to treatment failure of less than 2 months.  

The HPD rate rose to 12.8% when using the definition of RECIST progression and a twofold increase in TGR from before to during treatment. “In other words, patients with HPD are characterized by a twice higher percentage increase in volume per month during immunotherapy than before”, the researchers explain. 

The rate was 6.2% when HPD was defined as RECIST progression and at least a 50% increase in RECIST burden during therapy plus a twofold or greater increase in TGR during treatment.  

But it was 13.8% when defining HPD as RECIST progression and at least a 50% increase in the difference between TGR before and during treatment, “suggesting that the increase in volume per month during ICI therapy must be 50% higher than that expected with the increase before treatment”, they write. 

And finally, the HPD rate was 18.5% when it was defined using tumour growth kinetics based on diameter rather than volume, not accounting for a hypothesised exponential tumour growth, the team writes. 

Analysis indicated that concordance between the HPD definitions varied from 33.3% to 69.3%. 

All five HPD definitions gave a poorer outcome on landmark survival analysis for patients with HPD versus progressive disease (PD), with median overall survival (OS) durations of 3.4–6.0 months, depending on the definition used, versus 6.2–6.4 months.  

But the gap between the median OS of the HPD and PD groups varied from 0.2–3.0 months, “thus highlighting a disparity in the correlation of the different HPD definitions with outcomes”, the researchers say. 

Only when HPD was defined by progression pace, RECIST increase and time to treatment failure were the researchers able to significantly distinguish patients with HPD from those with PD only. 

And further analysis indicated that only when the index ΔTGR corresponded to a value above 100 were the researchers able to distinguish between HPD and PD patients in terms of median OS. 

“Therefore, to be in accordance with the concept of HPD that assumes both a high increase of the tumor kinetics and a poor survival outcome, the following definition based on our cohort would appear more relevant: RECIST percentage during therapy of greater than 20% […] and ΔTGR of greater than 100”, the team concludes. 

In an accompanying commentary, Rafael Santana-Davila, from the Fred Hutchinson Cancer Center in Seattle, Washington, USA, highlights that “one of the current limitations” for ICIs “is that we do not have a method of discerning which patients are more likely to benefit from these therapies or which are most likely to be harmed.” 

Describing further research into HPD as “paramount”, the commentator concludes: “Such efforts should include multiple cancer types, different lines of treatment, and tumor biopsies to identify both a possible biological explanation and biomarkers that can guide us in better selecting patients to limit adverse events and maximize benefits.” 

References  

Kas B, Talbot H, Ferrara R, et al. Clarification of definitions of hyperprogressive disease during immunotherapy for non-small cell lung cancer. JAMA Oncol; Advance online publication 11 June 2020. doi:10.1001/jamaoncol.2020.1634 

Santana-Davila R. Hyperprogressive disease after treatment with checkpoint inhibitors. Time for prospective studies. JAMA Oncol; Advance online publication 11 June 2020. doi:10.1001/jamaoncol.2020.1633