Platinum Priority – Kidney CancerEditorial by Camillo Porta, Alessandro Vercelli and Chiara Paglino on pp. 721–722 of this issueTumor Growth Rate Provides Useful Information to Evaluate Sorafenib and Everolimus Treatment in Metastatic Renal Cell Carcinoma Patients: An Integrated Analysis of the TARGET and RECORD Phase 3 Trial Data☆
Introduction
The introduction and recent revision of the Response Evaluation Criteria in Solid Tumors (RECIST) criteria have constituted a major improvement in the standardization of the response to antineoplastic agents in solid tumors [1], [2]. In this system, the patient's tumor burden is estimated by the sum of the longest diameters of the target lesions. The variation of the RECIST sum over a cycle of treatment is then transformed into a categorical variable to standardize the response to therapy (complete response, partial response, stable disease, and progressive disease). However, several authors have discussed the potential inadequacies of the RECIST criteria [3], [4], [5], [6], [7]. Those issues appear critical in the metastatic renal cell carcinoma (mRCC) setting, given the widespread use of registered molecular targeted agents (MTAs) such as antiangiogenics (sorafenib, sunitinib) or mammalian target of rapamycin inhibitors (everolimus, temsirolimus) [8], [9], [10], [11]. MTAs often induce long-lasting stable disease rather than tumor shrinkage and may even result in “pseudoprogression” images, rendering hazardous the use of RECIST [12], [13]. Innovative modalities to assess the drug response in the mRCC setting have been proposed but do not meet the adequate level of evidence to be applied in routine practice [14], [15].
The tumor growth rate (TGR) estimates the increase of the tumor volume over time [16], [17]. It incorporates the time between the imaging examinations, allowing for a quantitative and dynamic evaluation of the tumor response. However, how TGR is modified along the course of MTA and is associated with outcome in mRCC patients remain unknown. The present study was aimed at assessing whether TGR provides valuable clinical information for the management of mRCC patients as a prognostic factor and evaluating how TGR varies with two registered MTAs (sorafenib and everolimus).
Section snippets
Patients
The medical records of all patients prospectively enrolled in Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) phase 3 [8] (sorafenib vs placebo, n = 84) and in the RECORD phase 3 trial [10] (everolimus vs placebo, n = 43) at Gustave Roussy (IGR) were extracted. Using our institutional cohorts gave us the opportunity to access off-protocol additional imaging examinations performed before baseline or after progression to explore these washout periods (see Supplement). All
Description of the cohorts
The Motzer prognostic score, PFS, and OS of the cohorts of patients enrolled in TARGET (both in IGR and in the entire TARGET cohorts) and in the RECORD trial (IGR) are described in Table 1. The distributions of TGR across relevant treatment periods are described in Supplemental Table 1 and 2 and in Supplemental Figure 1.
Variation of tumor growth rate along clinically relevant treatment periods
At the first evaluation, whatever the treatment delivered (sorafenib or everolimus), nearly all evaluable patients from the IGR cohorts (28 of 29 sorafenib-treated patients and
Discussion
Although a number of publications have already introduced the TGR in various tumor types, TGR has not yet been translated into clinical use [16], [17], [19], [21], [22], [23], [24]. In our opinion, this study exhibits a strong potential for changing practices, showing that TGR provides useful information for the management of mRCC patients: (1) TGR is independently associated with prognosis in a large cohort of patients prospectively enrolled in a phase 3 clinical trial (n = 903), (2) TGR allows
Conclusions
The assessment of the TGR is feasible and simple to compute at bedside. Smartphone applications and Internet tools exist (http://www.gustaveroussy.fr/doc/tgr_calculator/index_en.html). Translating the TGR into clinical use could substantially change decision making for mRCC patients in several ways: improving the assessment of the prognosis, allowing for an earlier and more precise evaluation of the response to MTA, and giving an insight into the discontinuation period of the drugs. The TGR
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Early on-treatment tumor growth rate (EOT-TGR) determines treatment outcomes of advanced non-small-cell lung cancer patients treated with programmed cell death protein 1 axis inhibitor
2022, ESMO OpenCitation Excerpt :Several efforts have been made in other tumor entities to investigate predictive value of TGR upon early treatment in terms of outcomes of patients. Higher TGR during the first treatment cycle was found to be associated with shorter PFS and OS in patients with metastatic renal cell carcinoma treated with sorafenib or everolimus.30 Low TGR3m [TGR at 3 (±1) months of study entry] could be used as an early radiological predictor of favorable PFS and objective response in patients with advanced neuroendocrine tumors initiating systemic treatment.20,31
Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?
2020, Trends in CancerCitation Excerpt :TGR was evaluated in patients with metastatic renal cell carcinoma treated in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) (sorafenib vs placebo) and Renal Cell cancer treatment with Oral RAD001 given Daily (RECORD) (everolimus vs placebo) Phase III trials. Higher TGR (first cycle) was associated with worse PFS (HR 3.61; 95% CI 2.45–5.34) and worse OS (HR 4.69; 95% CI 1.54–14.39), independently from the Motzer score and from the treatment arm in the entire TARGET cohort [14]. Recently, in a control cohort with patients with NSCLC treated with chemotherapy, Ferrara et al. described a HPD rate of 14.2% (three of 21) (TGR >50%) in patients with PD as best response [3].
Tumor growth rate to assess therapy response to immune-based combinations for metastatic renal cell carcinoma
2024, Expert Review of Precision Medicine and Drug Development
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