Panitumumab Rechallenge in Chemorefractory Patients with Metastatic Colorectal Cancer

Hata, Akito; Katakami, Nobuyuki; Fujita, Shiro; Takatori, Kento; Horai, Aya; Kitajima, Naoto; Terashima, Kazuki

doi:10.1007/s12029-012-9453-7

Cited by 11 publications

(6 citation statements)

References 14 publications

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“…Notably, re-challenge with EGFR blockade was clinically effective and triggered partial responses or long lasting stabilization (Figure 3b and 3c). This is consistent with literature data showing that CRC patients can respond to anti-EGFR re-challenge 27 .…”

supporting

confidence: 93%

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Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients

Siravegna

Mussolin

Buscarino

et al. 2015

Nat Med

889

825

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Colorectal cancer (CRC) is a genetic disease governed by clonal evolution1. Genotyping CRC tissue is employed for therapeutic purposes but this approach has significant limitations. A tissue sample represents a single snapshot in time, is subjected to selection bias due to tumor heterogeneity, and can be difficult to obtain. We exploited circulating DNA (ctDNA) to genotype colorectal tumors and track clonal evolution during therapies with the anti-EGFR antibodies cetuximab or panitumumab. We identified genomic alterations in KRAS, NRAS, MET, ERBB2, FLT3, EGFR and MAP2K1 in ctDNA of patients with primary or acquired resistance to EGFR blockade. Mutant RAS clones, which rise in blood during EGFR blockade, decline upon withdrawal of anti-EGFR antibodies indicating that clonal evolution continues beyond clinical progression. Pharmacogenomic analysis of CRC cells, which had acquired resistance to cetuximab, reveals that upon antibody withdrawal KRAS clones decay, while the population regains drug sensitivity. ctDNA profiles of patients who benefit from multiple challenging with anti-EGFR antibodies exhibit pulsatile levels of mutant KRAS. These results reveal that the CRC genome adapts dynamically to intermittent drug schedules and provide a molecular explanation for the efficacy of re-challenge therapies based on EGFR blockade.

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supporting

confidence: 93%

“…In this regard discontinuous dosing strategy with BRAF inhibitors has been successfully attempted in preclinical models of BRAF driven melanomas 31 . Furthermore there is evidence that re-challenge with targeted therapies can be effective in patients with different tumors types 27,32–34 .…”

mentioning

confidence: 99%

Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients

Siravegna

Mussolin

Buscarino

et al. 2015

Nat Med

889

825

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“…The limited data on panitumumab rechallenge come from two case reports by Siravegna et al , 39 in which the patients achieved a partial response and stable disease when retreated with panitumumab following RAS mutational status switch and reversal. Additionally, Hata et al 108 describe two patients with good outcomes when retreated with panitumumab after a line of non-anti-EGFR therapy, although neither patient had experienced PD during prior panitumumab-based therapy (in the earlier line, one stopped panitumumab treatment due to toxicity, and the other had completed the determined number of panitumumab cycles). Finally, some reports have described responses to panitumumab treatment after failure of cetuximab, primarily in heavily pretreated patients.…”

Section: Introductionmentioning

confidence: 99%

Optimising the use of cetuximab in the continuum of care for patients with metastatic colorectal cancer

et al. 2018

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The anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in combination with chemotherapy is a standard of care in the first-line treatment of RAS wild-type (wt) metastatic colorectal cancer (mCRC) and has demonstrated efficacy in later lines. Progressive disease (PD) occurs when tumours develop resistance to a therapy, although controversy remains about whether PD on a combination of chemotherapy and targeted agents implies resistance to both components. Here, we propose that some patients may gain additional clinical benefit from the reuse of cetuximab after having PD on regimens including cetuximab in an earlier treatment line. We conducted a non-systematic literature search in PubMed and reviewed published and ongoing clinical trials, focusing on later-line cetuximab reuse in patients with mCRC. Evidence from multiple studies suggests that cetuximab can be an efficacious and tolerable treatment when continued or when fit patients with mCRC are retreated with it after a break from anti-EGFR therapy. Furthermore, on the basis of available preclinical and clinical evidence, we propose that longitudinal monitoring of RAS status may identify patients suitable for such a strategy. Patients who experience progression on cetuximab plus chemotherapy but have maintained RAS wt tumour status may benefit from continuation of cetuximab with a chemotherapy backbone switch because they have probably developed resistance to the chemotherapeutic agents rather than the biologic component of the regimen. Conversely, patients whose disease progresses on cetuximab-based therapy due to drug-selected clonal expansion of RAS-mutant tumour cells may regain sensitivity to cetuximab following a defined break from anti-EGFR therapy. Looking to the future, we propose that RAS status determination at disease progression by liquid, needle or excisional biopsy may identify patients eligible for cetuximab continuation and rechallenge. With this approach, treatment benefit can be extended, adding to established continuum-of-care strategies in patients with mCRC.

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“…Several reports on readministering anticancer drugs [8][9][10][11][12][13][14][15][16] have suggested that after a washout period, earlier-line drugs that were initially effective but then became ineffective might become effective again [11][12][13][14][15]. Santini et al reported cetuximab rechallenge to be significantly effective after a cetuximab-free interval with cytotoxic chemotherapy [13].…”

Section: Discussionmentioning

confidence: 99%

Readministration of Cancer Drugs in a Patient with Chemorefractory Metastatic Colorectal Cancer

Kawagoe

Ikeda

Oshiro

et al. 2020

Case Reports in Oncological Medicine

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A 63-year-old woman was admitted to our institution for severe pain in her right lower abdomen caused by the perforation of cecal cancer. She underwent emergency surgery, from which she was diagnosed with cecal carcinoma with liver, lung, and lymph node metastases. As she was taking aspirin to prevent cerebral infarction, anti-vascular endothelial growth factor (receptor) antibody and regorafenib therapy were not used. Thus, we started a modified FOLFOX 6+cetuximab regimen. This first-line treatment initially achieved a partial response (PR), but she then developed progressive disease (PD) after 14 months. We changed the regimen to FOLFIRI, followed by trifluridine/tipiracil, but her progression-free survival periods were 2.7 months and 1 month, respectively. Although we cycled through the available array of standard cancer drugs, the patient showed a good performance status, and some benefit from treatment still seemed plausible. We readministered the 5-fluorouracil oral preparation S-1, which maintained stable disease (SD) for 7 months. After PD emerged, we readministered the anti-epidermal growth factor receptor (EGFR) antibody panitumumab for 7.5 months of SD. Finally, 39 months after her diagnosis, she died from rapidly progressing disease. However, her relatively long survival implies that readministering drugs similar to those used in previous regimens might benefit patients with metastatic colorectal cancer.

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Panitumumab Rechallenge in Chemorefractory Patients with Metastatic Colorectal Cancer

Cited by 11 publications

References 14 publications

Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients

Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients

Optimising the use of cetuximab in the continuum of care for patients with metastatic colorectal cancer

Readministration of Cancer Drugs in a Patient with Chemorefractory Metastatic Colorectal Cancer

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