The following article features coverage from the IASLC 2019 World Conference on Lung Cancer meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Following a handful of case studies and small clinical trials that suggested immunotherapies were the likely source of hyperprogressive disease in some patients with cancer, new findings from a study in lung cancer appear to confirm that tumor hyperprogression may indeed be related to some immunotherapies. The findings were presented during a session at the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Barcelona, Spain.1

At this point, immune checkpoint inhibition involving PD-1/PD-L1 blockade — including studies with patients who were given nivolumab, pembrolizumab, atezolizumab, or durvalumab — has been shown to be associated with the promotion of tumor growth kinetics in certain patients with NSCLC and in some individuals with head and neck cancers.

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Some rapid progression observed in previous studies following a patient’s receipt of immunotherapies was determined to be temporary; in past trials, some patients who initially were found to have accelerated tumor growth appeared to experience symptom improvement and tumor shrinkage after they were treated with corticosteroid therapies. To confuse matters further, a small group of patients who received chemotherapy across these trials also saw their tumors grow in a hyperprogressive manner — leading some experts to question whether treatment-related hyperprogression was a real phenomenon.

The rapid time to metastasis that typically characterizes hyperprogression, which has historically been found to occur shortly following the receipt of immune checkpoint blockade in certain patients, has been somewhat hard to distinguish from the aggressive disease progression that can naturally occur in cancer. But in a retrospective study presented at WCLC 2019, researchers classified hyperprogression on the basis of the presence of 3 of 5 concomitant criteria: time to treatment failure of less than 2 months, an increase of 50% or higher in the sum of the diameters of target lesions between baseline and first radiological evaluation, appearance of a minimum of 2 new lesions in an already-involved organ between baseline and first radiological evaluation, spread of disease to a new organ between baseline and first radiological evaluation, and clinical deterioration with a decrease in Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 2 or more during the first 2 months of treatment with immune checkpoint blockade.

The investigators included patients with advanced non-small cell lung cancer (aNSCLC) who were treated between April 2013 and December 2019 at the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano in Italy, and were classified as having hyperprogressive disease (HPD) based on the clinical and radiological criteria from one of their prior studies.2 All patients who had received at least 1 cycle of immune checkpoint inhibitors (ICIs) were included, and patients were stratified by 4 categories: responders (57 cases, 22.2%), stable disease as best response (69 cases, 26.8%), progressive disease as best response (78 cases, 30.4%), or hyperprogressive disease (53 cases, 20.6%).

Clinicopathologic characteristics across groups were generally consistent, except as it related to a patient’s ECOG-PS: there was a higher rate of patients with an ECOG-PS score of more than 1 in the HPD subgroup (P =.0141).

At a median follow-up of 23.49 months, median progression-free survival was 14.2, 6.5, 2.3, and 1.5 months (P <.0001) and median overall survival was 32.5, 17.8, 7.8, and 4.1 months (P <.0001) in the responders, stable disease, progressive disease, and hyperprogressive disease groups, respectively. After adjusting for multiple variables between the patients in the progressive disease and hyperprogressive disease groups, the researchers confirmed that the patients in the hyperprogressive disease group had worse clinical outcomes than those in the progressive disease group.

The results led the researchers to conclude that regular progression was indeed different than hyperprogression, and that patients categorized as having hyperprogressive disease have worse outcomes. “The ICIs’ detrimental effect has to be taken into account and further investigated,” the authors wrote in the abstract.

Read more of Cancer Therapy Advisor‘s coverage of the IASLC annual meeting by visiting the conference page.

References
1. Lo Russo G, Signorelli D, Proto C, et al. Hyperprogressive disease in advanced non–small cell lung cancer patients treated with immune checkpoint inhibitors. Presented at: IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract OA14.06.
2. Lo Russo G, Moro M, Sommariva M, et al. Antibody-Fc/FcR interaction on macrophages as a mechanism for hyperprogressive disease in non-small cell lung cancer subsequent to PD-1/PD-L1 blockade. Clin Cancer Res. 2019;25(3):989-999.