VITAL phase 2 study: Upfront 5‐fluorouracil, mitomycin‐C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09‐02)

Feliú, Jaime; García‐Carbonero, Rocío; Capdevila, Jaume; Guasch, Inmaculada; Alonso-Orduna, V.; López, Carlos; García‐Alfonso, Pilar; Castañón, Carmen Luisa Pérez; Sevilla, Isabel; Cerezo, Laura; Conill, Carles; Quintana‐Angel, Begona; Sanchez, Maria E.; Ghanem, Ismael; Martı́n-Richard, Marta; López-Gómez, Miriam; León, Ana; Caro, M.; Fernández, Teresa; Maurel, Joan

doi:10.1002/cam4.2722

Cited by 12 publications

(8 citation statements)

References 43 publications

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“…Furthermore, seven patients de-escalated to maintenance therapy with cetuximab monotherapy with a median PFS of 13.8 months (95% CI, 7.24 to 20.25) and median OS of 31.4 months (95% CI, 21.73 to 40.98). Despite prior studies of anti-EGFR mAbs with CRT in the localized setting showing untoward toxicities, 30 , 31 the current analysis showed no grade 3 or 4 adverse events attributable to anti-EGFR therapy. 14 …”

Section: Discussioncontrasting

confidence: 80%

Metastatic or Locally Recurrent Anal Squamous Cell Carcinoma (SCAC): Current Clinical Trial Landscape and Novel Approaches

Rogers¹,

Leung²,

Johnson³

2022

CMAR

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Anal squamous cell carcinoma (SCAC) is a human papillomavirus (HPV) driven malignancy. Given inadequate HPV-vaccination rates, SCAC will continue to be a public health concern. SCAC is commonly diagnosed in the local or locoregional setting in which definitive chemoradiation provides the opportunity for cure and has high control rates. A minority of patients will develop recurrence or present with metastatic SCAC. Given the rarity of this disease, research has lagged compared to many other solid tumors. Historically, treatment has been based on extrapolating management approaches from more common squamous cell carcinoma malignancies and/or small case series or case reports. Fortunately, dedicated prospective clinical trial investigation in the advanced setting has emerged in recent years. Here, we review the current strategies for treatment along with remaining challenges and viable next steps for the management of metastatic SCAC.

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Section: Discussioncontrasting

confidence: 80%

Metastatic or Locally Recurrent Anal Squamous Cell Carcinoma (SCAC): Current Clinical Trial Landscape and Novel Approaches

Rogers¹,

Leung²,

Johnson³

2022

CMAR

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“…The VITAL study (GEMCAD-09-02, NCT01285778), a phase II multicenter, single-arm study, aimed to assess the efficacy and safety of panitumumab in combination with the standard treatment of localized ASCC tumors (5-fluorouracil (5FU), mitomycin C and radiotherapy). However, the conclusion of this trial was that the panitumumab addition to standard chemotherapy increased toxicity and did not improve patients’ outcomes 19 . In this work, we have studied samples from this clinical trial and from a cohort treated only with chemoradiotherapy to define possible mechanisms of resistance and to suggest how to select patients in future studies.…”

Section: Introductionmentioning

confidence: 85%

Description of the genetic variants identified in a cohort of patients diagnosed with localized anal squamous cell carcinoma and treated with panitumumab

Trilla-Fuertes¹,

Gámez‐Pozo

Maurel

et al. 2021

Sci Rep

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Squamous cell carcinoma is the most frequent histologic type of anal carcinoma. The standard of care since the 1970s has been a combination of 5-fluorouracil, mitomycin C, and radiotherapy. This treatment is very effective in T1/T2 tumors (achieving complete regression in 80–90% of tumors). However, in T3/T4 tumors, the 3-year relapse free survival rate is only 50%. The VITAL trial aimed to assess the efficacy and safety of panitumumab in combination with this standard treatment. In this study, 27 paraffin-embedded samples from the VITAL trial and 18 samples from patients from daily clinical practice were analyzed by whole-exome sequencing and the influence of the presence of genetic variants in the response to panitumumab was studied. Having a moderate- or high-impact genetic variant in PIK3CA seemed to be related to the response to panitumumab. Furthermore, copy number variants in FGFR3, GRB2 and JAK1 were also related to the response to panitumumab. These genetic alterations have also been studied in the cohort of patients from daily clinical practice (not treated with panitumumab) and they did not have a predictive value. Therefore, in this study, a collection of genetic alterations related to the response with panitumumab was described. These results could be useful for patient stratification in new anti-EGFR clinical trials.

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“…28 HPV16 infection and several clinical factors as neutrophilia or anemia have also been reported as related to OS and/or DFS. 14,29,30 Regarding gene-based biomarkers, p53-positive tumors have a shorter DFS. 31,32 Moreover, p21, nuclear factor-κB, Ki67, and cyclin A levels have been associated with prognosis in ASCC.…”

Section: Discussionmentioning

confidence: 99%

“…This study was approved by the ethical committee of Hospital Universitario La Paz (PI‐1926) and written informed consent was obtained for all the participants in the study. Twenty‐seven patients from the VITAL clinical trial study (GEMCAD‐09‐02, NCT01285778), were treated with panitumumab, 5‐FU, MMC, and radiotherapy 14 . The other 18 patients were included from the routine clinical practice at Hospital Universitario La Paz and Hospital Clinic and were treated with cisplatin–5‐FU or MMC–5‐FU and concomitant radiotherapy.…”

Section: Methodsmentioning

confidence: 99%

Utility ofCYP2D6copy number variants as prognostic biomarker in localized anal squamous cell carcinoma

Trilla-Fuertes

Gámez‐Pozo

Nogué

et al. 2023

Cancer

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Background: Anal squamous cell carcinoma (ASCC) is an infrequent tumor whose treatment has not changed since the 1970s. The aim of this study is the identification of biomarkers allowing personalized treatments and improvement of therapeutic outcomes.Methods: Forty-six paraffin tumor samples from ASCC patients were analyzed by whole-exome sequencing. Copy number variants (CNVs) were identified and their relation to disease-free survival (DFS) was studied and validated in an independent retrospective cohort of 101 ASCC patients from the Multidisciplinary Spanish Digestive Cancer Group (GEMCAD). GEMCAD cohort proteomics allowed assessing the biological features of these tumors.Results: On the discovery cohort, the median age was 61 years old, 50% were males, stages I/II/III: 3 (7%)/16 (35%)/27 (58%), respectively, median DFS was 33 months, and overall survival was 45 months. Twenty-nine genes whose duplication was related to DFS were identified. The most representative was duplications of the CYP2D locus, including CYP2D6, CYP2D7P, and CYP2D8P genes. Patients with CYP2D6 CNV had worse DFS at 5 years than those with two CYP2D6 copiesThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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VITAL phase 2 study: Upfront 5‐fluorouracil, mitomycin‐C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09‐02)

Abstract: DFS rate at 3 y 61.1 (47.1, 72.4) OS rate at 3 y 78.4 (65.1, 87.1) CFS rate at 3 y 68.1 (54.2, 78.6) Clinical CR rate 81.0 (69.8, 92.2) LRF-free rate at 3 y 64.8 (50.9, 75.7) Distant failure free rate, at 3 y 93.0 (82.4, 97.3) RFS rate at 3 y 75.8 (60.5, 85.8)

Cited by 12 publications

References 43 publications

Metastatic or Locally Recurrent Anal Squamous Cell Carcinoma (SCAC): Current Clinical Trial Landscape and Novel Approaches

Metastatic or Locally Recurrent Anal Squamous Cell Carcinoma (SCAC): Current Clinical Trial Landscape and Novel Approaches

Description of the genetic variants identified in a cohort of patients diagnosed with localized anal squamous cell carcinoma and treated with panitumumab

Utility ofCYP2D6copy number variants as prognostic biomarker in localized anal squamous cell carcinoma

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