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Hyperprogressive disease in advanced non–small cell lung cancer patients treated with immune checkpoint inhibitors


Hyperprogressive disease ( HPD ) is a paradoxical boost in tumour growth described in a subset of cancer patients treated with immune checkpoint inhibitors ( ICIs ).

Researchers retrospectively collected data about all consecutive patients with advanced non-small cell lung cancer ( aNSCLC ) treated with immune checkpoint inhibitors at Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Italy ) between 04/2013 and 12/2018.
Patients were classified according to our previously published clinical / radiological criteria for HPD ( Lo Russo G, Clin Canc Res 2018 ).
All immune checkpoint inhibitors administered for greater than or equal to 1 cycle were admitted.

301 cases were reviewed and 257 were evaluable for response.

Researchers identified four categories: responders ( R, 57 cases, 22.2% ), patients with stable disease as best response ( SD, 69 cases, 26.8% ), patients with progressive disease as best response ( P, 78 cases, 30.4% ) and patients with HPD ( 53 cases, 20.6% ).

Clinical / pathological variables were uniformly distributed among groups, except for a higher rate of patients with ECOG performance status more than 1 in HPD group ( p = 0.0141 ).

After a median follow-up of 23.49 months ( IQR 10.72–44.21 months ), median progression-free survival ( mPFS ) and median overall survival ( mOS ) were 14,2 vs 6,5 vs 2,3 vs 1,5 months ( p less than 0.0001 ) and 32,5 vs 17,8 vs 7,8 vs 4,1months ( p less than 0.0001 ) in responder, stable disease, progressive disease and hyperprogressive disease group, respectively.

The multivariate analyses, between progressive disease and hyperprogressive disease groups, adjusted for ICIs line, number of metastatic sites and ECOG-PS according to progression-free survival ( hazard ratio, HR 2.448, 95% CI 2.137-2.899, p less than 0.0001 ) and overall survival ( HR 2.481, 95%CI 2.092-2.950, p less than 0.0001 ) confirmed the worse outcome of hyperprogressive disease group.

In conclusion, the updated analysis confirmed patients with hyperprogressive disease as a distinct category that performs significantly worse than other groups, including patients with progressive disease.
The incidence of hyperprogressive disease in the cohort is relevant.
The immune checkpoint inhibitors’ detrimental effect has to be taken into account and further investigated. ( Xagena )

Source: IASLC 2019 World Conference on Lung Cancer

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