Κυριακή 19 Νοεμβρίου 2017

HYPER-PROGRESSION-A NOT SO RARE "ADVERSE EVENT" OF IMMUNOTHERAPY

With all the excitement over the improved survival seen in some patients with cancer treated with immunotherapy, little attention has been paid to the other side of the coin: the fact that some patients get worse.
This phenomenon, referred to as hyperprogressive disease, was highlighted recently in a presentation here at the 18th World Conference on Lung Cancer (WCLC).
Hyperprogressive disease describes an acceleration in tumor growth, as measured on computed tomography, wherein the tumor grows at a faster rate during treatment than the rate at which it was growing before treatment started.
It has previously been described with immunotherapy (reported in 9% of patients with advanced cancer), but until now there have been no data on this phenomenon in patients with lung cancer.  
At the meeting, researchers from the Institut Gustave Roussy, Villejuif, France, led by Roberto Ferrara, MD, presented data from a retrospective analysis of patients they had treated with advanced non-small cell lung cancer (NSCLC). 
They looked specifically for hyperprogressive disease and found it occurred in 14% of patients with advanced NSCLC receiving immunotherapy (single-agent programed cell death inhibitors) and in 5% of patients receiving single-agent chemotherapy.
The figures come from two different sets of patients. From the retrospective analysis of patients with advanced NSCLC who had received immunotherapy at eight different institutions over a period of 5 years (2012 to 2017), the researchers collected data on 333 evaluable patients, with a median follow-up of 12 months.  
Among these patients, 19% had a complete response or partial response to immunotherapy, 39% had stable disease, 42% had progressive disease, 5% had pseudo-progressive disease, and 14% had hyperprogressive disease.
In this subgroup of 56 patients with hyperprogressive disease, tumor growth was accelerated while they were receiving immunotherapy, Dr Ferrara said at the meeting.
This hyperprogressive disease was also associated with pluri-metastatic disease and appearance of new lung lesions, the researchers note.
These patients also had a worse survival than the overall patient population; the median overall survival (OS) was 13 months in the total population but only 3.4 months in the subgroup of patients with hyperprogressive disease. This was even worse than in the subgroup of patients who had progressive disease, for whom the median OS was 5.4 months, which was "as expected" for this group, Dr Ferrara commented.   
The researchers then looked at another group of patients with advanced NSCLC who had received single-agent chemotherapy (most of whom received a taxane; a third of these patients were receiving chemotherapy as third-line treatment, Dr Ferrara noted).
This retrospective analysis included 59 patients with a median follow-up of 26 months. It found that 10% of patients had a complete response or partial response to chemotherapy, 31% had stable disease, 59% had progressive disease, 0% had pseudoprogressive disease, and 5% had hyperprogressive disease. 
The median OS in this population was 8 months, but in the subgroup with hyperprogressive disease it was only 4.5 months.  This was not significantly different from the median OS of 3.9 months seen in the subgroup of progressive disease, Dr Ferrara noted.
In conclusion, Dr Ferrara emphasized that patients with hyperprogressive disease have a shorter survival and noted again the median OS of only 3.4 months with immunotherapy in this subgroup.
Approached for comment, H. Jack  West, MD, medical director of the Thoracic Oncology Program at the Swedish Cancer Institute in Seattle, Washington, told Medscape Medical News: "I think this is interesting and adds some actual data in an area in which we've only had clinical observation/anecdotal experience. But I don't think it really changes how we treat patients — just an indication that a subset of patients are actually harmed by immunotherapy. However, there's no reliable way to identify these patients in advance."
Dr West discusses these new data in some detail in a video. He says the French researchers should be congratulated for this study, which characterizes the phenomenon of hyperprogressive disease in patients with lung cancer receiving immunotherapy for the first time.
The findings should give us "a moment of pause," for they show that not all patients benefit from immunotherapy, and in fact "a significant minority may be harmed," Dr West comments.  
Dr Ferrara and colleagues reported no disclosures. Dr West reports serving as a consultant for Genentech/Roche, Merck & Co, and Clovis Oncology
18th World Conference on Lung Cancer (WCLC). Abstract MA 10.11. Presented on October 17, 2017.

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