Clarification of Definitions of Hyperprogressive Disease During Immunotherapy for Non–Small Cell Lung Cancer

Kas, Baptiste; Talbot, Hugues; Ferrara, Roberto; Richard, Clément; Lamarque, Jean-Philippe; Pitre-Champagnat, Stéphanie; Planchard, David; Balleyguier, Corinne; Besse, Benjamin; Mezquita, Laura; Lassau, Nathalie; Caramella, Caroline

doi:10.1001/jamaoncol.2020.1634

Cited by 75 publications

(85 citation statements)

References 20 publications

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“…When using the second method for evaluation of tumor growth (ΔTGR) as previously proposed [ 11 ], we found a statistically difference in PFS between hyperprogressors and non-hyperprogressors (median PFS 1.8 months (95% CI, 1.51–2.08) vs. 3.1 months (95% CI, 1.29–4.90) respectively, p = 0.002), but no difference in OS (median OS 11.06 (95 % CI, 0–22.58) in patients with HPD vs. 12.53 months (95% CI, 8.27–16.78) in patients with non-HPD, p = 0.674).…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, Kato et al and Matos et al used a mixture of clinical and radiological criteria by incorporating TTF < 2 months in HPD definition [ 21 , 22 ]. In an attempt to comprehensively compare and unify different definitions of HPD, Kas et al analyzed all methodologies of previous HPD definitions and applied them to a cohort of patients with NSCLC [ 11 ]. Interestingly, the authors observed several differences in the rate of HPD depending on the method used; in addition, they showed that only a minority of patients (4.7%) were covered by all definitions, suggesting that each methodology includes a distinct subgroup of patients with diverse patterns of tumor progression [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…The authors suggested a new definition of HPD based on the difference between TGR before and during immunotherapy (ΔTGR) that was found to best correlate with poor OS. A ΔTGR of more than 100 was indicated to distinguish between patients with HPD and patients with PD that was not classified as HPD [ 11 ]. When this definition of HPD was applied in our cohort, no significant difference in survival was found; however, the study by Kas et al and previous studies included patients with NSCLC and other solid tumors, and this definition might not reflect the complex tumor biology and growth kinetics of HNSCC.…”

Section: Discussionmentioning

confidence: 99%

“…HPD was defined as the presence of TGKR ≥ 2. A second method for the evaluation of tumor growth was used as previously described [ 11 ]. ΔTGR was calculated and the proposed cut-off of 100 was used.…”

Section: Methodsmentioning

confidence: 99%

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Patterns of Response to Immune Checkpoint Inhibitors in Association with Genomic and Clinical Features in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC)

Economopoulou

Anastasiou

Papaxoinis

et al. 2021

Cancers

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Background: We sought to compare patterns of response to immune checkpoint inhibitors (ICI) with respect to clinical and genomic features in a retrospective cohort of patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Methods: One hundred seventeen patients with R/M HNSCC treated with ICI were included in this study. Tumor growth kinetics (TGK) prior to and TGK upon immunotherapy (IO) was available for 49 patients. The TGK ratio (TGKR, the ratio of tumor growth velocity before and upon treatment) was calculated. Hyperprogression (HPD) was defined as TGKR ≥ 2. Results: HPD was documented in 18 patients (15.4% of the whole cohort). Patients with HPD had statistically significant shorter progression free survival (PFS) (median PFS 1.8 months (95% CI, 1.03–2.69) vs. 6.1 months for patients with non-HPD (95% CI, 4.78–7.47), p = 0.0001) and overall survival (OS) (median OS 6.53 months (95% CI, 0–13.39) vs. 15 months in patients with non HPD (95% CI, 7.1–22.8), p = 0.0018). In a multivariate Cox analysis, the presence of HPD remained an independent prognostic factor (p = 0.049). Primary site in the oral cavity and administration of ICI in the second/third setting were significant predictors of HPD in multivariate analysis (p = 0.028 and p = 0.012, respectively). Genomic profiling revealed that gene amplification was more common in HPD patients. EGFR gene amplification was only observed in HPD patients, but the number of events was inadequate for the analysis to reach statistical significance. The previously described MDM2 amplification was not identified. Conclusions: HPD was observed in 15.4 % of patients with R/M HNSCC treated with IO and was associated with worse PFS and OS. EGFR amplification was identified in patients with HPD.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Patterns of Response to Immune Checkpoint Inhibitors in Association with Genomic and Clinical Features in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC)

Economopoulou

Anastasiou

Papaxoinis

et al. 2021

Cancers

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“…On the other hand, it has been suggested that irAEs could help select responders to ICB in bladder cancer (17). Secondly, some patients experience an acceleration of tumor growth kinetics with poor survival called hyperprogression which, at present, remains difficult to characterize (18,19).…”

Section: Characterizing the Immune Function In The Response To Checkpmentioning

confidence: 99%

Therapy-Induced Modulation of the Tumor Microenvironment: New Opportunities for Cancer Therapies

et al. 2020

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Advances in immunotherapy have achieved remarkable clinical outcomes in tumors with low curability, but their effects are limited, and increasing evidence has implicated tumoral and non-tumoral components of the tumor microenvironment as critical mediators of cancer progression. At the same time, the clinical successes achieved with minimally invasive and optically-guided surgery and image-guided and ablative radiation strategies have been successfully implemented in clinical care. More effective, localized and safer treatments have fueled strong research interest in radioimmunotherapy, which has shown the potential immunomodulatory effects of ionizing radiation. However, increasingly more observations suggest that immunosuppressive changes, metabolic remodeling, and angiogenic responses in the local tumor microenvironment play a central role in tumor recurrence. In this review, we address challenges to identify responders vs. non-responders to the immune checkpoint blockade, discuss recent developments in combinations of immunotherapy and radiotherapy for clinical evaluation, and consider the clinical impact of immunosuppressive changes in the tumor microenvironment in the context of surgery and radiation. Since the therapy-induced modulation of the tumor microenvironment presents a multiplicity of forms, we propose that overcoming microenvironment related resistance can become clinically relevant and represents a novel strategy to optimize treatment immunogenicity and improve patient outcome.

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Hyperprogression in Patients With Cancer Receiving Immune Checkpoint Inhibitors

Sehgal

2021

JAMA Netw Open

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The development of immune checkpoint inhibitors has revolutionized the field of cancer therapeutics, but it has also brought to forefront the issue of optimal assessment of clinical benefit during treatment with these agents. The use of these immune-activating drugs often can be associated with atypical patterns of therapeutic response, ranging from hyperprogression, pseudoprogression, and dissociated or mixed response to durable clinical responses long after discontinuation of therapy. 1 Hyperprogression, which reflects unexpectedly rapid progression of disease in patients receiving immunotherapy (with clinically deleterious implications), has been a topic of intense discussion among oncologists. 2,3 With publication of multiple clinical reports of different cancer types worldwide, hyperprogression is now accepted by most oncologists to be a true phenomenon rather than natural progression of disease. 1,3 However, major limitations remain in the literature, particularly with regard to heterogeneity in assessment criteria used to define hyperprogression, the retrospective nature of analyses, and the lack of a comparator group in most studies of this phenomenon.Park and colleagues 4 present the results of a systematic review of hyperprogression and a meta-analysis of its incidence in patients with solid malignant neoplasms receiving immune checkpoint inhibitors, while summarizing the current challenges with regard to assessment of hyperprogressive disease. The authors have analyzed data from 24 studies, including 16 retrospective studies, 5 studies with retrospective analysis of clinical trials, and 2 prospective cohort studies, to report a 13.3% (95% CI, 10.1%-16.5%) pooled incidence of hyperprogression. Of note, the range of this incidence was wide (5.9% to 43.1%), reflecting the heterogeneity of the patient population studied and the definitions used for assessment. Those studies that reported survival outcomes found an association between hyperprogression and poor prognosis. 2,4 More importantly, shorter overall survival was reported in most studies of patients with hyperprogressive disease compared with those with natural disease progression without hyperprogression, 4-6 further underscoring the clinical importance of hyperprogression.Definitions for hyperprogression vary substantially in the literature. Park and colleagues 4 used common definitions of hyperprogression to divide the studies in their analysis into 4 broad assessment criterion categories: (1) tumor growth rate ratio, (2) tumor growth kinetics ratio, (3) early tumor burden increase, and (4) a combination of the other categories. The reported pooled incidence of hyperprogression in these 4 subgroups range from 9.4% to 20.6%. Furthermore, the authors highlighted various challenges in accurately detecting hyperprogressive disease with these nonuniform criteria, including the lack of consideration of development of new lesions or changes in nontarget lesions; lack of consensus regarding optimal time for imaging assessment; discrepancy with the common...

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Clarification of Definitions of Hyperprogressive Disease During Immunotherapy for Non–Small Cell Lung Cancer

Cited by 75 publications

References 20 publications

Patterns of Response to Immune Checkpoint Inhibitors in Association with Genomic and Clinical Features in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC)

Patterns of Response to Immune Checkpoint Inhibitors in Association with Genomic and Clinical Features in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC)

Therapy-Induced Modulation of the Tumor Microenvironment: New Opportunities for Cancer Therapies

Hyperprogression in Patients With Cancer Receiving Immune Checkpoint Inhibitors

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