Hyperprogressive disease (HPD) is frequent in non-small cell lung cancer (NSCLC) patients (pts) treated with anti PD1/PD-L1 monoclonal antibodies (IO)

Ferrara, Roberto; Caramella, Caroline; Texier, Matthieu; Valette, C. Audigier; Tessonnier, Laurent; Mezquita, Laura; Lahmar, J.; Mazières, Julien; Zalcman, Gérard; Brosseau, Solenn; Westeel, Virginie; Moulec, Sylvestre Le; Leroy, Laura; Duchemann, Boris; Veillon, Rémi; Planchard, David; Boucher, Mathieu; Koscielny, Serge; Soria, J-C.; Besse, Benjamin

doi:10.1093/annonc/mdx380.009

Cited by 30 publications

(37 citation statements)

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“…In one study, 40 (16%) of 242 patients with advanced NSCLC were reported to have hyperprogressive disease (HPD). Despite similar clinical, molecular and pathological characteristics, including PD-L1 status, patients with HPD had significantly poorer survival outcomes compared with those without HPD [69]. In this study, the response to treatment prior to receiving immunotherapy was also similar between patients who developed HPD and those who did not.…”

Section: Ecog Performance Statusmentioning

confidence: 55%

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

et al. 2018

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Immune checkpoint inhibitors targeting PD-1 or PD-L1 represent a standard treatment option for patients with advanced non-small-cell lung cancer. However, a substantial proportion of patients will not benefit from these treatments, and robust biomarkers are required to help clinicians select patients who are most likely to benefit. Here, we discuss the available evidence on the utility of clinical characteristics in the selection of patients with advanced non-small-cell lung cancer as potential candidates for single-agent anti-PD-1/PD-L1 therapy, and provide practical guidance to clinicians on identifying those patients who are most likely to benefit. Recommendations on the use of immune checkpoint inhibitor in clinically challenging populations are also provided.

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Section: Ecog Performance Statusmentioning

confidence: 55%

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

et al. 2018

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“…While immunotherapy can produce a significant and durable response in patients with NSCLC, physicians caring for patients on these agents must be cognizant of the potential for an aggressive pattern of accelerated progression in a subset of patients. This pattern of rapid progression may lead to diminished progression free and OS (5,9). HPD is an increasingly recognized phenomenon for which positive predictive variables, other than possibly advanced age, have not yet been identified.…”

Section: Discussionmentioning

confidence: 99%

“…Some patients on immunotherapy may experience a rapid paradoxical progression of tumor with worsening clinical status, which appears to negatively impact survival (5,9,10). This phenomenon has been termed HPD.…”

Section: Hyperprogressive Disease (Hpd)mentioning

confidence: 99%

Hyperprogressive disease in patients with non-small cell lung cancer on immunotherapy

Kurman

Murgu

2018

J. Thorac. Dis.

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Immunotherapy agents in metastatic non-small cell lung cancer (NSCLC) can result in improved quality of life and survival when compared with platinum-based chemotherapy. Novel response patterns such as pseudoprogression and hyperprogression, however, have been described and pose a challenge to treating physicians. Predictors of hyperprogressive disease (HPD) have not yet been identified. Evaluation and management by a multidisciplinary team involving medical and radiation oncologists, thoracic radiologists, and proceduralists is necessary to identify this subset of patients in a timely manner. Repeat biopsy distinguishes HPD from pseudoprogression and may eventually elucidate predictive biomarkers. We describe the epidemiology of these two phenomena, their diagnostic criteria, and their relevance for interventional pulmonologists.

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“…However, in a subset of patients, ICI paradoxically accelerates tumor growth, a phenomenon known as hyperprogression (HP; refs. [3][4][5][6]. Studies have estimated that the prevalence of HP in patients with different cancer histotypes treated with ICI may range between 9% and 29% (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5][6]. Studies have estimated that the prevalence of HP in patients with different cancer histotypes treated with ICI may range between 9% and 29% (3)(4)(5)(6). No significant histopathologic and molecular features capable of predicting a priori HP have been identified, with the partial exception of rare MDM2 amplification and EGFR mutations (5).…”

Section: Introductionmentioning

confidence: 99%

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

Russo

Moro

Sommariva

et al. 2019

Clinical Cancer Research

334

371

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Hyperprogression (HP), a paradoxical boost in tumor growth, was described in a subset of patients treated with immune checkpoint inhibitors (ICI). Neither clinicopathologic features nor biological mechanisms associated with HP have been identified. Among 187 patients with non-small cell lung cancer (NSCLC) treated with ICI at our institute, cases with HP were identified according to clinical and radiologic criteria. Baseline histologic samples from patients treated with ICI were evaluated by IHC for myeloid and lymphoid markers. T-cell-deficient mice, injected with human lung cancer cells and patient-derived xenografts (PDX) belonging to specific mutational subsets, were assessed for tumor growth after treatment with antibodies against mouse and human programmed death receptor-1 (PD-1). The immune microenvironment was evaluated by flow cytometry and IHC. Among 187 patients, 152 were evaluable for clinical response. We identified four categories: 32 cases were defined as responders (21%), 42 patients with stable disease (27.7%), 39 cases were defined as progressors (25.7%), and 39 patients with HP (25.7%). Pretreatment tissue samples from all patients with HP showed tumor infiltration by M2-like CD163CD33PD-L1 clustered epithelioid macrophages. Enrichment by tumor-associated macrophages (TAM) was observed, even in tumor nodules from immunodeficient mice injected with human lung cancer cells and with PDXs. In these models, tumor growth was enhanced by treatment with anti-PD-1 but not anti-PD-1 F(ab) fragments. These results suggest a crucial role of TAM reprogramming, upon Fc receptor engagement by ICI, eventually inducing HP and provide clues on a distinctive immunophenotype potentially able to predict HP.

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Hyperprogressive disease (HPD) is frequent in non-small cell lung cancer (NSCLC) patients (pts) treated with anti PD1/PD-L1 monoclonal antibodies (IO)

Cited by 30 publications

References 0 publications

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

Hyperprogressive disease in patients with non-small cell lung cancer on immunotherapy

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

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