Phase II APEC trial: The impact of primary tumor side on outcomes of first‐line cetuximab plus FOLFOX or FOLFIRI in patients with <i>RAS</i> wild‐type metastatic colorectal cancer

Price, Timothy; Shen, Lin; B.Y., Brigette; Esser, Regina; Chen, Wenfeng; Gibbs, Peter; Lim, Robert; Cheng, Ann‐Lii

doi:10.1111/ajco.13154

Cited by 6 publications

(6 citation statements)

References 13 publications

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“…A meta‐analysis of the PRIME and CRYSTAL studies found that patients with RAS wild‐type mutations with left‐sided tumors experienced a survival benefit with cetuximab (OS: HR for left‐sided tumors, .69 [95% CI, .58%–.83%]; p < .0001 and HR for right‐sided tumors, .96 [95% CI, .68%–1.35%]; p = .802) 17 . Similar findings were reported in the tumor location subanalysis of the Phase II APEC clinical study 18 . The OPTIM1SE study supports these findings, demonstrating a consistent HR for OS favoring left‐ vs right‐sided primary tumors in patients receiving first‐line cetuximab‐based 5‐FU regimens (HR, .69 [95% CI, .49%–.99%]; p = .042).…”

Section: Discussionsupporting

confidence: 69%

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Prospective, open‐label, and observational study of cetuximab for metastatic colorectal carcinoma: The OPTIM1SE study

Yang

Chen

Lin

et al. 2023

Asia-Pac J Clncl Oncology

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AimThe OPTIM1SE study observed long‐term real‐world outcomes of cetuximab‐based infusional 5‐fluorouracil (5‐FU) regimens for first‐line treatment of metastatic colorectal cancer (mCRC) across Asia‐Pacific and Middle East regions, aiming to characterize their use, effectiveness, and safety in routine practice.MethodsOPTIM1SE was a prospective, open‐label, observational study. Patients with untreated KRAS wild‐type mCRC and distant metastases were treated per locally approved labels and monitored for 3 years via electronic medical records. The primary endpoint was the overall response rate (ORR). Secondary endpoints included safety, progression‐free survival (PFS), and overall survival (OS).ResultsFrom November 19, 2013, to June 30, 2016, 520 patients were enrolled in 51 sites. Patients were mostly male (61.2%), with a mean age of 58.5 (±12.0) years; 420 patients received leucovorin, 5‐FU, and irinotecan–based regimens and 94 received leucovorin, 5‐FU, and oxaliplatin. The most common primary tumor site was the rectum (38.8%), with liver metastases (65.0%). ORR was 45.4% (95% CI, 41.1%–49.7%), including 26 patients (5.0%) with a complete response. Median PFS was 9.9 months (95% CI, 8.2–11.0); median OS (mOS) was 30.8 months (95% CI, 27.9–33.6). Higher mOS was associated with tumors of left compared with right‐sided origin (hazard ratio, 0.69 [95% CI, 0.49–0.99]); higher ORR was also associated with liver metastases compared with all other metastases (55.4% vs. 40.2%). Adverse events were consistent with the known safety profile of cetuximab.ConclusionCetuximab‐based 5‐FU regimens were effective first‐line treatments for mCRC in routine practice, particularly in patients with left‐sided disease and liver metastases only.

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Section: Discussionsupporting

confidence: 69%

“…17 Similar findings were reported in the tumor location subanalysis of the Phase II APEC clinical study. 18 The OPTIM1SE study supports these findings, demonstrating a consistent HR for OS favoring left-vs right-sided primary tumors in patients receiving firstline cetuximab-based 5-FU regimens (HR, .69 [95% CI, .49%-.99%]; p = .042).…”

Section: Discussionmentioning

confidence: 63%

Prospective, open‐label, and observational study of cetuximab for metastatic colorectal carcinoma: The OPTIM1SE study

Yang

Chen

Lin

et al. 2023

Asia-Pac J Clncl Oncology

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“…Those mutations can appear in oncogenes, tumor suppressor genes and genes related to DNA repair mechanisms [3]. Current treatment for CRC involves a variety of approaches, including surgery and radiotherapy, as well as the use of chemotherapeutic drugs such as FOLFOX and FOLFIRI [4][5][6]. Additionally, monoclonal antibodies or proteins against vascular endothelial growth factor (VEGF) and epidermal growth receptor (EGFR) combined with traditional chemotherapy have been applied to improve the outcome of CRC [7].…”

Section: Introductionmentioning

confidence: 99%

HSPA4 knockdown retarded progression and development of colorectal cancer

Zhang

Dai

et al. 2020

Preprint

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Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of cancer death. The heat shock 70kDa protein 4 (HSPA4) participate in progression and development of cancers. However, the cellular functions, potential molecular mechanisms of HSPA4 in CRC are still largely unknown. Methods: In this study, qRT-PCR and Western Blot were used to identify the constructed HSPA4 knockdown cell lines, which was further used to construct mouse xenotransplantation models. Effects of HSPA4 knockdown on cell proliferation, apoptotic, cell cycle and migration of CRC were examined using Celigo cell counting assay, Flow cytometry, wound healing assay and Transwell assay, respectively. In addition, Human Apoptosis Antibody Array was performed to explore downstream molecular mechanism of HSPA4 in CRC cells. Results: HSPA4 was overexpressed in CRC, which was positively associated with lymphatic metastasis (N value), number of Lymph node. In addition, high expression of HSPA4 predicted poor prognosis of patients with CRC. Furthermore, HSPA4 knockdown inhibit proliferation, migration, promote apoptosis, and arrest cell cycle of CRC cells in vitro. Moreover, in vivo results supported HSPA4 knockdown inhibit tumor growth. Additionally, the induction of apoptosis of CRC cells by HSPA4 knockdown required the participation of a series of apoptosis-related proteins. The downregulation of HSPA4 promoted the progression of CRC cells, which resulted in alterations of PI3K/Akt, CCND1 and CDK6 in downstream signaling pathways. Conclusions: In sum, the downregulation of HSPA4 promoted CRC and may be a potential target for molecular therapy.

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“…So far, chemotherapy is the primary treatment for inhibiting colon cell proliferation and angiogenesis. However, the emergence of some anti-tumor drugs has provided more treatment options to be used in combination with chemotherapy including bevacizumab, cetuximab, and vemurafenib monoclonal antibodies, which block the activity of VEGF and Ras/Raf and inactivate the MAPK and PI3K/AKT pathways to improve survival in patients with metastatic colorectal cancer ( 17 ). In recent years, Chinese medicine has drawn continuous attention due to its positive effects in the treatment of various diseases.…”

Section: Discussionmentioning

confidence: 99%

Ligustrazine inhibits the viability and motility of colon cancer cells

Chen¹,

Yang²,

Mu³

et al. 2020

Transl Cancer Res TCR

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Background Despite the advances in the diagnosis and treatment of colon cancer, the disease remains a major threat worldwide. Ligustrazine (LSZ) is an alkaloid with anti-tumor activity. This study aimed to elucidate the anti-tumor qualities of LSZ on colon cancer cells in vitro and vivo , as well as its involved mechanism. Methods In this study, CCK-8, colony formation, transwell invasion assay and flow cytometry were employed to examined the cells behaviors. Moreover, the proteins related to the epithelial mesenchymal transformation (EMT) process were determined by RT-qPCR and western blotting. Then, the expression of PI3K, AKT, and mTOR were tested by western blotting. Furthermore, a xenograft mouse model was used to investigate the role of LSZ in vivo . Results LSZ treatment (0.1, 0.5 and 1.5 mM) significantly inhibited SW480 cells’ efforts to proliferate, migrate and invade and also induced SW480 cell apoptosis. In addition, LSZ inhibited EMT process. Meanwhile, Western blotting indicated that LSZ treatment administered on a dose-dependent basis inhibited the phosphorylation of PI3K, AKT, and mTOR. Furthermore, in our animal experiments, the weight of colon cancer was significantly lower in LSZ-treated mice than in untreated ones, and the expression of Ki67 and N-cadherin positive cells was significantly lower in the treated mice than in their control group counterparts. Conclusions Together, the results suggested that LSZ inhibited proliferation, motility, and EMT of colon cancer cells through the PI3K/AKT/mTOR pathway in vitro and in vivo .

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Phase II APEC trial: The impact of primary tumor side on outcomes of first‐line cetuximab plus FOLFOX or FOLFIRI in patients with RAS wild‐type metastatic colorectal cancer

Cited by 6 publications

References 13 publications

Prospective, open‐label, and observational study of cetuximab for metastatic colorectal carcinoma: The OPTIM1SE study

Prospective, open‐label, and observational study of cetuximab for metastatic colorectal carcinoma: The OPTIM1SE study

HSPA4 knockdown retarded progression and development of colorectal cancer

Ligustrazine inhibits the viability and motility of colon cancer cells

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