EGFR amplification (amp) and survival in the REAL-3 trial

Smyth, Elizabeth; Kouvelakis, Kyriakos; Cunningham, David; Hahne, Jens C.; Peckitt, Clare; Vlachogiannis, George; Watkins, David; S, Rao; Starling, Naureen; Wilson, Sanna Hulkki; Waddell, Tom; Okines, Alicia; Crosby, Tom; Mansoor, Wasat; Wadsley, Jonathan; Middleton, Gary; Wotherspoon, Andrew; Chau, Ian; Valeri, Nicola

doi:10.1093/annonc/mdy282.030

Cited by 2 publications

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“…15 In the REAL-3 trial, EGFR amplification showed a trend, although statistically non-significant, that correlated with worse PFS and OS independent of the regimen given to patients with gastroesophageal adenocarcinomas. 16 EGFR amplification status was examined in TRANS-COG and showed survival benefits for this subgroup with the addition of gefitinib as second-line treatment. 17 In this trial, only 25% of the patients had a diagnosed ESCC.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER)

et al. 2020

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Background: Palliative chemotherapy of advanced oesophageal squamous cell cancer (ESCC) consists of cisplatin/5fluorouracil (CF) to target epidermal growth factor receptor (EGFR) with panitumumab (P); chemotherapy enhanced overall survival (OS) in advanced colorectal or squamous cell head and neck cancers. With prospective serum and tumour biomarkers, we tested if P added to CF (CFP) improved OS in advanced ESCC. Patients and methods: Eligible patients with confirmed ESCC that was not curatively resectable or did not qualify for definitive radiochemotherapy, were randomised 1 : 1 to receive CF [cisplatin (C) 100 mg/m 2 i.v., day 1; 5-fluorouracil (F) 1000 mg/m 2 i.v., days 1e4] or CF plus P (9 mg/kg, i.v., day 1, each q3-week cycle) until progressive disease or unacceptable toxicity. Safety was reviewed by the Data Safety Monitoring Board after 40, 70 and 100 patients who completed at least one cycle. After 53 enrolled patients, cisplatin was reduced from 100 mg/m 2 to 80 mg/m 2. Results: The trial was stopped early based on interim efficacy results triggered by the third safety analysis: median OS (mOS) favoured CF over CFP, regardless of cisplatin dose [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.06e2.98; P ¼ 0.028]. In the final analysis, mOS was 10.2 versus 9.4 months for CF versus CFP, respectively (HR 1.17, 95% CI 0.79 e1.75; P ¼ 0.43). One hundred (70.4%) of 142 patients in the safety population died, 51 (51.0%) with CFP. Most deaths were related to disease progression [44/49 (90%) deaths in CF versus 34/51 (67%) deaths in CFP]; objective responses [27/73 (37.0%)] were identical. The most common serious adverse events were kidney injury [3 (4.3%) versus 7 (9.7%)], general health deterioration [5 (7.1%) versus 5 (6.9%)] and dysphagia [4 (5.7%) versus 4 (5.6%)] in CF versus CFP, respectively. There were three (4.3%) and 17 (23.6%) common terminology criteria for adverse events (CTCAE) grade 5 events in CF versus CFP, respectively. Low soluble (s)EGFR levels were associated with better progression-free survival; sEGFR was induced under CFP. Conclusion: EGFR inhibition added to CF did not improve survival in unselected advanced ESCC patients. The results support further liquid biopsy studies. Trial registration: ClinicalTrials.gov (NCT01627379) and EudraCT (2010-020606-15).

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Section: Discussionmentioning

confidence: 99%

Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER)

et al. 2020

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“…Patients with EGFR -amplified tumors trended non-significantly towards having inferior progression-free and overall survival, regardless of treatment arm, suggesting that EGFR amplification portends a worse prognosis. Even in patients with tissue or plasma ddPCR EGFR:CNTNAP2 copy number ratio > 2 (6.2%) or > 5 (2.7%), the addition of panitumumab failed to prolong progression-free and overall survival ( 58 ). One explanation is that these disappointing results reflect an interaction between panitumumab and an epirubicin-containing chemotherapy regimen, as all phase 2 and 3 mEG trials adding EGFR inhibition to an anthracycline triplet trended towards inferior survival ( 38 , 42 , 47 , 53 ).…”

Section: Targeting Egfr In Metastatic Egc (Megc)mentioning

confidence: 99%

Targeting EGFR in Esophagogastric Cancer

Maron

Janjigian

2020

Front. Oncol.

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Esophagogastric cancer (EGC) remains a major cause of cancer-related mortality. Overall survival in the metastatic setting remains poor, with few molecular targeted approaches having been successfully incorporated into routine care to-date: only first line anti-HER2 therapy in ERBB2-expressing tumors, second line anti-VEGFR2 therapy with ramucirumab in unselected patients, and pembrolizumab in PD-L1 expressing or MSI-H patients. EGFR inhibitors were extensively studied in EGC, including phase III trials with cetuximab (EXPAND), panitumumab (REAL3), and gefitinib (COG). All three trials were conducted in unselected populations, and therefore, failed to demonstrate clinical benefit. Here, we review previous attempts at targeting EGFR in EGC and potential future biomarkers for targeting this pathway in patients with EGFR-amplified tumors.

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EGFR amplification (amp) and survival in the REAL-3 trial

Cited by 2 publications

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Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER)

Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER)

Targeting EGFR in Esophagogastric Cancer

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