Early tumor shrinkage after first-line medical treatment of metastatic colorectal cancer: a meta-analysis

Colloca, Giuseppe; Venturino, Antonella; Guarneri, Domenico

doi:10.1007/s10147-019-01405-1

Cited by 10 publications

(10 citation statements)

References 40 publications

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“…Systemic chemotherapy with anti-epidermal growth factor receptor (EGFR) antibody and chemotherapy without molecular targeted drugs is introduced as soon as possible after SEMS placement in patients with wild-type RAS and RAS mutation, respectively. Early tumor shrinkage (ETS) 6-8 weeks after chemotherapy introduction, which is a reliable surrogate marker for better survival [71], is evaluated, and primary tumor resection is planned for patients with ETS. Primary tumor resection in patients with ETS at this time point prevents delayed SEMS-related complications and is associated with longer survival, with the additional effect of bevacizumab administration in patients with the RAS mutation.…”

Section: Our Therapeutic Strategy For Systemic Chemotherapy After Semmentioning

confidence: 99%

Systemic Chemotherapy is a Promising Treatment Option for Patients with Colonic Stents: A Review

Matsuda

Yamada

Matsumoto

et al. 2021

J Anus Rectum Colon

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Approximately 10% of patients with colorectal cancer (CRC) develop malignant large bowel obstruction (MLBO) at diagnosis. Furthermore, for 35% of patients with MLBO, curative primary tumor resection is unfeasible because of locally advanced disease and comorbidities. The practice of placing a self-expandable metallic stent (SEMS) has dramatically increased as an effective palliative treatment. Recent advances in systemic chemotherapy for metastatic CRC have significantly contributed to prolonging patients' prognosis and expanding the indications. However, the safety and efficacy of systemic chemotherapy in patients with SEMS have not been established. This review outlines the current status of this relatively new therapeutic strategy and future perspectives. Some reports on this topic have demonstrated that 1) systemic chemotherapy and the addition of molecular targeted agents contribute to prolonged survival in patients with SEMS; 2) delayed SEMS-related complications are a major concern, and this requires strict patient monitoring; however, primary tumor control by chemotherapy might result in decreased complications, especially regarding re-obstruction; and 3) using bevacizumab could be a risk factor for SEMS-related perforation, which may be lethal. Although this relatively new approach for unresectable stage IV obstructive CRC requires a well-planned clinical trial, this therapy could be promising for patients who are unideal candidates for emergency surgery and require immediate systemic chemotherapy.

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Section: Our Therapeutic Strategy For Systemic Chemotherapy After Semmentioning

confidence: 99%

Systemic Chemotherapy is a Promising Treatment Option for Patients with Colonic Stents: A Review

Matsuda

Yamada

Matsumoto

et al. 2021

J Anus Rectum Colon

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“…[10][11][12][13][14][15] Of interest is that ETS is available more rapidly than conventionally used best response criteria according to Response Evaluation Criteria in Solid Tumors (RECIST); and RECIST defines Open access responders by a 30% reduction in the sum-of-longest diameters (SLD) of target-lesions, yet prognostic information may be identifiable across the range. [10][11][12][13][14][15] Further, ETS may be a potential biomarker for go, no-go decisions in clinical trials. 9 Regarding ICIs, the appropriateness of RECIST has been questioned considering observations of pseudoprogression and hyper-progression, and it is unclear if these concerns apply to ETS.…”

Section: Introductionmentioning

confidence: 99%

Early tumor shrinkage identifies long-term disease control and survival in patients with lung cancer treated with atezolizumab

Hopkins

Kichenadasse

Karapetis

et al. 2020

J Immunother Cancer

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BackgroundPreliminary evidence indicates that early tumor shrinkage (ETS) following immune checkpoint inhibitor (ICI) initiation may be associated with survival outcomes in patients with advanced melanoma. ETS has not been explored as a biomarker of survival outcomes or patient-reported outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs.MethodsThe study pooled data from patients with NSCLC in the randomized trials OAK and POPLAR (atezolizumab vs docetaxel; n=1464), and single-arm atezolizumab trials BIRCH and FIR (n=797). The association between ETS (≥10% decrease in pretreatment sum-of-longest diameters of target-lesions at 6 weeks) and overall survival (OS), progression-free survival (PFS), time to deterioration (TDD) in health-related quality-of-life (HRQoL) and physical function (PF) was assessed using Cox proportional hazard analysis.ResultsETS occurred in 20% of atezolizumab-treated patients with NSCLC within OAK and POPLAR and was associated with highly favorable OS (HR 0.33, p<0.001), PFS (HR 0.31, p<0.001), TDD in HRQoL (HR 0.73, p=0.01) and PF (HR 0.52, p<0.001). The results were replicated in the BIRCH and FIR data. Atezolizumab-treated patients achieving ETS had markedly improved OS compared with docetaxel-treated patients achieving ETS (24-month OS 55% vs 32%); PFS was also markedly improved (24-month PFS 31% vs 4%). In contrast, for patients not achieving ETS, atezolizumab-treatment was associated with more modest OS (24-month OS 23% vs 20%) and PFS (24-month PFS 3% vs 1%) improvement compared with docetaxel. Overall, the effect size for ETS within the atezolizumab-treated patients was significantly greater than that in the docetaxel-treated patients (P(interaction)=0.002 for OS and P(interaction)<0.001 for PFS).ConclusionsETS is an easily measurable biomarker, predictive of highly favorable survival and patient-reported outcomes with atezolizumab treatment for advanced NSCLC. Further, ETS identifies patients with significantly greater treatment benefit for ICI therapy.

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“…12,13 Furthermore, the link between the early tumor shrinkage (ETS) and overall survival or progression free-survival has been proposed as an early efficacy marker based on several studies. [14][15][16] Nonlinear mixed effect models (NLMEM) are increasingly used to support drug decision making, especially in early-phase trials. 17 In oncology, these models can be used to capture the pharmacokinetics of antitumoral agents or biomarker kinetics.…”

Section: How Might This Change Drug Discovery De-velopment And/or Tmentioning

confidence: 99%

“…However, in the field of modeling and simulation it seems preferable to use the continuous TS data when available rather than RECIST as this would result in a loss of information 12,13 . Furthermore, the link between the early tumor shrinkage (ETS) and overall survival or progression free‐survival has been proposed as an early efficacy marker based on several studies 14–16 …”

mentioning

confidence: 99%

Comparison of Various Phase I Combination Therapy Designs in Oncology for Evaluation of Early Tumor Shrinkage Using Simulations

Seurat

Girard

Goteti

2020

CPT Pharmacom & Syst Pharma

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There is still a lack of efficient designs for identifying the dose response in oncology combination therapies in early clinical trials. The concentration response relationship can be identified using the early tumor shrinkage time course, which has been shown to be a good early response marker of clinical efficacy. The performance of various designs using an exposure–tumor growth inhibition model was explored using simulations. Different combination effects of new drug M and cetuximab (reference therapy) were explored first assuming no effect of M on cetuximab (to investigate the type I error (α)), and subsequently assuming additivity or synergy between cetuximab and M. One‐arm, two‐arm, and four‐arm designs were evaluated. In the one‐arm design, 60 patients received cetuximab + M. In the two‐arm design, 30 patients received cetuximab and 30 received cetuximab + M. In the four‐arm design, in addition to cetuximab and cetuximab + M as standard doses, combination arms with lower doses of cetuximab were evaluated (15 patients/arm). Model‐based predictions or “simulated observations” of early tumor shrinkage at week 8 (ETS8) were compared between the different arms. With the same number of individuals, the one‐arm design showed better statistical power than other designs but led to strong inflation of α in case of misestimated reference for ETS8 value. The two‐arm design protected against this misestimation and, with the same total number of subjects, would provide higher statistical power than a four‐arm design. However, a four‐arm design would be helpful for exploring more doses of cetuximab in combination with M to better understand the interaction.

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Early tumor shrinkage after first-line medical treatment of metastatic colorectal cancer: a meta-analysis

Cited by 10 publications

References 40 publications

Systemic Chemotherapy is a Promising Treatment Option for Patients with Colonic Stents: A Review

Systemic Chemotherapy is a Promising Treatment Option for Patients with Colonic Stents: A Review

Early tumor shrinkage identifies long-term disease control and survival in patients with lung cancer treated with atezolizumab

Comparison of Various Phase I Combination Therapy Designs in Oncology for Evaluation of Early Tumor Shrinkage Using Simulations

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