Clinical outcome and molecular characterisation of chemorefractory metastatic colorectal cancer patients with long-term efficacy of regorafenib treatment

Martinelli, Erika; Sforza, Vincenzo; Cardone, Claudia; Capasso, Anna; Nappi, Anna; Martini, Giulia; Napolitano, Stefania; Rachiglio, Anna Maria; Normanno, Nicola; Cappabianca, Salvatore; Reginelli, Alfonso; Bisceglie, M. Di; Latiano, Tiziana Pia; Maiello, Evaristo; Orditura, Michele; Vita, F. De; Morgillo, Floriana; Troiani, Teresa

doi:10.1136/esmoopen-2017-000177

Cited by 30 publications

(24 citation statements)

References 11 publications

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“…Finally, as recently reported in a study from our Institution on a consecutive series of 123 patients with chemorefractory mCRC treated with regorafenib, a good ECOG PS and a long history of metastatic disease were significantly associated with better clinical outcome from regorafenib. 12 The current analysis seems to confirm a trend between the good ECOG PS and response to TAS-102 (p=0.08), supporting the concept that patients with mCRC in good clinical conditions, even though heavily pretreated with all available treatment options for first and second line, could obtain a significant clinical benefit with TAS-102.…”

Section: Discussionsupporting

confidence: 74%

Clinical outcome of patients with chemorefractory metastatic colorectal cancer treated with trifluridine/tipiracil (TAS-102): a single Italian institution compassionate use programme

et al. 2017

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BackgroundTAS-102 improves overall survival (OS) in patients with metastatic colorectal cancer (mCRC) refractory to standard treatments. However, predictive biomarkers of efficacy are currently lacking.Patients and methodsWe treated a cohort of 43 chemorefractory mCRC patients treated with TAS-102, in a single institution expanded access, compassionate use programme. We stratified patients in two groups according to number of cycles received (<6 cycles and ≥6 cycles). OS, progression-free survival (PFS) and safety were evaluated.ResultsThirteen out of 43 patients (30%) obtained a clinically relevant disease control with TAS-102 therapy. Eleven of them were treated for ≥6 cycles with TAS-102, reaching a median PFS of 7.5 months (95% CI 5.8 to 9.2 months) and a median OS of 11.2 months (95% CI range not reached yet). A trend towards significance (p=0.08) between a good performance status and response to TAS-102 was observed. Further, 7 out of the 11 TAS-102 long-treated patients achieved a clinical benefit from a previous treatment with regorafenib. A significant correlation between regorafenib and TAS-102 clinical efficacy was observed (p=0.008). Six out 13 regorafenib-naïve patients were treated with regorafenib after progression from TAS-102. All these patients achieved SD with a median duration of treatment with regorafenib of 6.1 months (range, 1.6–6.7).ConclusionPatients with mCRC in good clinical conditions, even though having been heavily pretreated with all the available treatment options, could obtain a significant clinical benefit from treatment with TAS-102. Moreover, a previous clinical benefit obtained with regorafenib is potentially predictive of clinical efficacy of subsequent TAS-102 treatment.

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Section: Discussionsupporting

confidence: 74%

Clinical outcome of patients with chemorefractory metastatic colorectal cancer treated with trifluridine/tipiracil (TAS-102): a single Italian institution compassionate use programme

et al. 2017

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“…A biopsy of a liver lesion was obtained and was analysed by NGS for a panel of 143 genes (see online supplementary appendix A for details). 17 HER2 gene amplification (with 70% allele frequency) was confirmed, while a novel TP53 p.R175H gene mutation (c.524G>A, 70.4% allele frequency) was found. No mutations or amplifications were found in KRAS, NRAS, BRAF, AKT, PIK3CA, EGFR, HER3, MET as well as in other genes that could be involved in HER family-activated pathways.…”

Section: Resultsmentioning

confidence: 86%

“…The first biopsy (from laterocervical lymph node metastasis) was analysed with the Ion AmpliSeq Colon and Lung Cancer Panel (Life Technologies) using Ion Torrent semiconductor sequencing, as previously reported 15 16 (see online supplementary appendix A for details). The second biopsy (from one of the liver metastases) was analysed by using a more extensive targeted high-multiplex PCR-based NGS panel (OncoMine Comprehensive Assay), as previously described 17 (see online supplementary appendix A for details).…”

Section: Methodsmentioning

confidence: 99%

Sequential HER2 blockade as effective therapy in chemorefractory, HER2 gene-amplified, RAS wild-type, metastatic colorectal cancer: learning from a clinical case

et al. 2018

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BackgroundConstitutive activation of HER2-dependent intracellular signalling by HER2 gene amplification or by HER2 mutations has been demonstrated as a mechanism of primary and secondary cancer resistance to cetuximab or panitumumab in preclinical and clinical models of metastatic colorectal cancer (mCRC). Both HER2 Amplification for Colorectal Cancer Enhanced Stratification (HERACLES) cohort A and My Pathway clinical trials provided clinical evidence that anti-HER2 therapies could be active in these patients.Patient and methodsHER2 gene amplification and HER2 protein overexpression analysis were performed in tumour tissue by fluorescence in situ hybridisation and immunohistochemistry. HER2 positivity was defined according to HERACLES CRC-specific HER2 scoring criteria. DNA analysis for multiple assessment of gene mutations or amplifications was carried out with the next-generation sequencing (NGS) Ion AmpliSeq Colon and Lung Cancer Panel and by using a more extensive targeted high-multiplex PCR-based NGS panel (OncoMine Comprehensive Assay).ResultsWe report the clinical case of a patient with HER2 gene amplified and RAS/BRAF wild-type mCRC who experienced a long lasting and relevant clinical efficacy from sequential anti-HER2 therapies (trastuzumab plus lapatinib, pertuzumab plus trastuzumab, trastuzumab emtansine, trastuzumab plus capecitabine) achieving a cumulative clinical benefit of 29 months, after failure of the first three lines of standard treatments, which included all the potentially active drugs in mCRC, and which accounted for only 14 months of disease control. HER gene amplification was confirmed by NGS on two different metastatic lesions during the evolution of the disease.ConclusionThe clinical case highlights the role of HER2 gene amplification as a key genetic driver of cancer development and progression in mCRC and suggests that sequential HER2 blockade could be a potential therapeutic strategy.

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“…Regular follow-up can be considered for asymptomatic patients with isolated lung metastases, particularly patients with small metastases (e.g., lesions < 1 cm) and good prognosis. Regorafenib may be a choice after failure with first-line and second-line treatment [49]. Please refer to the 2017 National Health and Family Planning Commission Chinese Protocol of Diagnosis and Treatment of Colorectal Cancer for specific drug options [22].…”

Section: Management Of Synchronous Lung Metastasesmentioning

confidence: 99%

Expert consensus on multidisciplinary therapy of colorectal cancer with lung metastases (2019 edition)

Yuan

Yang

et al. 2019

J Hematol Oncol

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The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts’ clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases. Electronic supplementary material The online version of this article (10.1186/s13045-019-0702-0) contains supplementary material, which is available to authorized users.

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Clinical outcome and molecular characterisation of chemorefractory metastatic colorectal cancer patients with long-term efficacy of regorafenib treatment

Cited by 30 publications

References 11 publications

Clinical outcome of patients with chemorefractory metastatic colorectal cancer treated with trifluridine/tipiracil (TAS-102): a single Italian institution compassionate use programme

Clinical outcome of patients with chemorefractory metastatic colorectal cancer treated with trifluridine/tipiracil (TAS-102): a single Italian institution compassionate use programme

Sequential HER2 blockade as effective therapy in chemorefractory, HER2 gene-amplified, RAS wild-type, metastatic colorectal cancer: learning from a clinical case

Expert consensus on multidisciplinary therapy of colorectal cancer with lung metastases (2019 edition)

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