Hyperprogression—Immunotherapy-Related Phenomenon vs Intrinsic Natural History of Cancer—In Reply

Ferrara, Roberto; Caramella, Caroline; Besse, Benjamin

doi:10.1001/jamaoncol.2019.0138

Cited by 6 publications

(2 citation statements)

References 6 publications

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“…3,4,11 A comparison between tumor growth kinetics before and after ICI initiation is mandatory to distinguish between HPD and the intrinsic natural history of aggressive cancers. 12 In this regard, an expert panel has recently highlighted the importance of prebaseline radiologic assessment to measure the inflection point in the slope of tumor kinetics. 13 However, the use of sizedependent criteria (ie, TGR, RECIST, SLD) may not be applicable for patients rapidly progressing with nonmeasurable lesions (ie, lymphangitis, bone metastases, pleural and peritoneal effusions).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Fast-Progression, Hyperprogressive Disease, and Early Deaths in Advanced Non–Small-Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or Chemotherapy

Ferrara

Mezquita

Texier

et al. 2020

JCO Precision Oncology

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PURPOSE Hyperprogressive disease (HPD), fast progression (FP), and early death (ED) have been described in 13.8%, 4.7%, and 5.6% and in 5.1%, 2.8%, and 6.8%, respectively, of patients with non–small-cell lung cancer (NSCLC) treated with single-agent programmed cell death ligand 1 inhibitors (ICI) or chemotherapy, respectively. Whether FP/ED and HPD represent overlapping patterns is unknown. PATIENTS AND METHODS FP, ED, and HPD were retrospectively assessed in patients with NSCLC treated with single-agent ICI or chemotherapy. Eligibility required 2 computed tomography (CT) scans before and 1 CT scan during treatment. (1) HPD, (2) FP, (3) ED were defined as (1) RECIST version 1.1 progression at first CT scan and tumor growth rate variation per month > 50%, (2) ≥ 50% increase in the sum of the longest diameters of target lesions within 6 weeks from baseline, and (3) death as a result of radiologic progression within 12 weeks from baseline CT scan, respectively. RESULTS Of 406 ICI-treated NSCLC, 56 patients (13.8%), 9 patients (2.2%), and 36 patients (8.8%) were HPD, FP, and ED, respectively. Eight (14.2%) and 20 (35.7%) of 56 patients with HPD were also FP and ED. ED significantly correlated with baseline Eastern Cooperative Oncology Group performance status ≥ 2 compared with HPD (33% v 13%, P = .02). Overall survival was significantly longer for HPD (3.4 months [95% CI, 2.7 to 4.0 months]) compared with FP (0.7 months [95% CI, 0.6 to 0.8 months]); HR, 0.18 [95% CI, 0.08 to 0.42]; P < .0001) and ED (1.4 months [95% CI, 1.3 to 1.6 months]); HR, 0.19 [95% CI, 0.11 to 0.34]); P < .0001), whereas it did not differ between FP and ED (HR, 1.3 [95% CI, 0.56 to 3.0]; P = .55). Of 59 patients with NSCLC treated with single-agent chemotherapy, the HPD, FP, and ED rates were 5.1%, 1.7%, and 6.7%, respectively. CONCLUSION FP, ED, and HPD represent distinct progression patterns with limited overlap and different survival outcomes.

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Section: Discussionmentioning

confidence: 99%

Comparison of Fast-Progression, Hyperprogressive Disease, and Early Deaths in Advanced Non–Small-Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or Chemotherapy

Ferrara

Mezquita

Texier

et al. 2020

JCO Precision Oncology

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“…To this point, the phenomenon of treatment-induced accelerated tumor growth-previously termed hyperprogressive disease (HPD)-was reported to be a new pattern of progression in patients receiving monotherapy with CPIs targeting programmed cell death 1 ligand 1 (PD-L1) or programmed cell death 1 protein (PD-1). [1][2][3][4][5][6] HPD has generally been defined as a tumor growth rate (TGR) from baseline to the first evaluation that is ≥2fold that of a reference TGR established by two consecutive pretreatment scans. Because there is no consensus on an optimal way to assess this phenomenon, alternative criteria have been reported.…”

Section: Introductionmentioning

confidence: 99%

Fast progression in non–small cell lung cancer: results from the randomized phase III OAK study evaluating second-line atezolizumab versus docetaxel

Gandara

Reck

Moro-Sibilot

et al. 2021

J Immunother Cancer

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BackgroundTreatment-induced accelerated tumor growth is a progression pattern reported with immune checkpoint inhibitors that has never been evaluated in randomized phase III studies because it requires two pretreatment scans. This study aimed to develop clinically relevant and applicable criteria for fast progression (FP), incorporating tumor growth kinetics and early death from disease progression to analyze data from the randomized phase III OAK study.MethodsThe OAK study evaluated the efficacy and safety of atezolizumab versus docetaxel as second-line or third-line treatment for stage IIIb/IV non–small cell lung cancer. FP rates and associated baseline factors were analyzed. FP was defined as either a ≥50% increase in the sum of largest diameters (SLDs) within 6 weeks of treatment initiation or death due to cancer progression within 12 weeks (absent post-baseline scan).ResultsForty-two of 421 patients (10%) receiving atezolizumab and 37 of 402 (9%) receiving docetaxel had FP. Twenty patients with FP (48%) receiving atezolizumab versus 12 (30%) receiving docetaxel had a ≥50% SLD increase within 6 weeks. FP was significantly associated with an ECOG (Eastern Cooperative Oncology Group) performance status of 1 (vs 0), ≥3 metastatic sites at baseline, and failure of preceding first-line treatment within 6 months, but not with epidermal growth factor receptor mutation, programmed cell death 1 ligand 1 or tumor mutational burden. Overall survival in patients with FP and a ≥50% SLD increase at week 6 was similar with atezolizumab and docetaxel (unstratified HR 0.89 (95% CI 0.41 to 1.92)).ConclusionsFP rates were similar with atezolizumab and docetaxel in the OAK study, suggesting that FP may not be unique to checkpoint inhibitors, although the underlying mechanisms may differ from those of chemotherapy. Applying the FP criteria to other phase III checkpoint inhibitor trials may further elucidate the risk factors for FP.Trial registration numberNCT02008227.

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Hyperprogressive Disease upon Immune Checkpoint Blockade: Focus on Non–small Cell Lung Cancer

et al. 2020

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Hyperprogression—Immunotherapy-Related Phenomenon vs Intrinsic Natural History of Cancer—In Reply

Abstract: Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

Cited by 6 publications

References 6 publications

Comparison of Fast-Progression, Hyperprogressive Disease, and Early Deaths in Advanced Non–Small-Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or Chemotherapy

Comparison of Fast-Progression, Hyperprogressive Disease, and Early Deaths in Advanced Non–Small-Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or Chemotherapy

Fast progression in non–small cell lung cancer: results from the randomized phase III OAK study evaluating second-line atezolizumab versus docetaxel

Hyperprogressive Disease upon Immune Checkpoint Blockade: Focus on Non–small Cell Lung Cancer

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