Relationships between tumour response and primary tumour location, and predictors of long-term survival, in patients with RAS wild-type metastatic colorectal cancer receiving first-line panitumumab therapy: retrospective analyses of the PRIME and PEAK clinical trials

Peeters, Marc; Price, Timothy; Taieb, Julien; Geißler, Michael; Rivera, Fernando; Canon, Jean-Luc; Pentheroudakis, George; Koukakis, Reija; Burdon, Peter; Siena, Salvatore

doi:10.1038/s41416-018-0165-z

Cited by 32 publications

(38 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Baseline patient demographics and disease characteristics by ETS status for the subgroup of patients who were symptomatic at baseline (29% [194/659]) are shown in Supplemental Table 3 in the online version. The existence of tumor-related symptoms at baseline was associated with a poorer prognosis; OS was reduced in these patients compared to patients with no symptoms at baseline (median [95% CI], 21 Figure 3B).…”

Section: Time To New Symptomatic Events By Ets and Dpr For Patients Wmentioning

confidence: 99%

“…Left-sided tumors are more common and are associated with a better prognosis and increased response to anti-EGFR treatment. [20][21][22] First-line panitumumab treatment has been associated with improved ETS and DpR compared to comparator treatments in patients with left-sided disease. 21 Further to this, existence of ETS !…”

Section: Introductionmentioning

confidence: 99%

“…[20][21][22] First-line panitumumab treatment has been associated with improved ETS and DpR compared to comparator treatments in patients with left-sided disease. 21 Further to this, existence of ETS ! 30% may identify patients with right-sided tumors that might respond to panitumumab.…”

Section: Introductionmentioning

confidence: 99%

“…30% may identify patients with right-sided tumors that might respond to panitumumab. 21 In addition to tumor response, patients' QoL and tumor-related symptoms should be factored into treatment decisions in mCRC. 2 Common tumor-related symptoms of advanced cancer include pain, anorexia, fatigue, and asthenia.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Relationship Between Tumor Response and Tumor-Related Symptoms in RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses From 3 Panitumumab Trials

Taieb

Geißler

Rivera

et al. 2019

Clinical Colorectal Cancer

Self Cite

View full text Add to dashboard Cite

Tumor-related symptoms can affect treatment choices in metastatic colorectal cancer (mCRC). In the current study, 659 patients with RAS wild-type mCRC were retrospectively analyzed to evaluate the relationship between tumor shrinkage and the time to onset of tumor-related symptoms. Symptom onset was delayed in patients with earlier and greater tumor shrinkage. Therefore, treatments that facilitate cytoreduction may delay symptom development. Background: There is no standardized assessment of symptomatic events in metastatic colorectal cancer (mCRC) despite disease symptoms that affect treatment decisions. Data from 3 first-line panitumumab in mCRC trials were retrospectively analyzed to assess whether early tumor shrinkage (ETS) and depth of response (DpR) were associated with time to occurrence of tumor-related symptoms. Patients and Methods: Patients with RAS wild-type mCRC from PRIME, PEAK, and Study 314 were included. ETS was defined as a reduction of ! 30% in the sum of the longest diameters of lesions at 8 weeks. DpR was calculated as maximum percentage change in tumor size from baseline to nadir. The proportion of patients who developed symptoms (including a composite symptomatic endpoint) during study treatment was calculated. This study was registered at ClinicalTrials.gov as PRIME (NCT00364013), PEAK (NCT00819780), and Study 314 (NCT00508404). Results: Overall, data of 659 patients were analyzed. Onset of symptoms was delayed in patients with ETS ! 30% versus ETS < 30% and in patients with greater DpR. In patients with symptoms at baseline who experienced ETS ! 30%, overall survival was similar to that seen for patients without symptoms at baseline. Conclusion: Both ETS and DpR were associated with delayed onset of symptoms in RAS wildtype mCRC patients. Treatments with high cytoreductive potential may delay symptom development.

show abstract

Section: Time To New Symptomatic Events By Ets and Dpr For Patients Wmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Relationship Between Tumor Response and Tumor-Related Symptoms in RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses From 3 Panitumumab Trials

Taieb

Geißler

Rivera

et al. 2019

Clinical Colorectal Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…44 Several studies have shown more favourable tumour shrinkage with anti-EGFR therapy than with bevacizumab for right-sided tumours, suggesting that anti-EGFR antibodies could provide a means of achieving rapid control of tumour volume for certain classes of right-sided tumours. 45 Transcriptional biomarkers have also been studied in association with cetuximab efficacy (table 2). Upregulation of a specific microRNA, miR-31-3p, plays a significant role in activating RAS signalling and was identified as a potential negative predictor of cetuximab efficacy in the FIRE-3 study.…”

Section: Introductionmentioning

confidence: 99%

Current challenges in the implementation of precision oncology for the management of metastatic colorectal cancer

Kim

2020

ESMO Open

View full text Add to dashboard Cite

Over the last few decades, molecularly targeted agents have been used for the treatment of metastatic colorectal cancer. They have made remarkable contributions to prolonging the lives of patients. The emergence of several biomarkers and their introduction to the clinic have also aided in guiding such treatment. Recently, next-generation sequencing (NGS) has enabled clinicians to identify these biomarkers more easily and reliably. However, there is considerable uncertainty in interpreting and implementing the vast amount of information from NGS. The clinical relevance of biomarkers other than NGS are also subjects of debate. This review covers controversial issues and recent findings on such therapeutics and their molecular targets, including VEGF, EGFR, BRAF, HER2, RAS, actionable fusions, Wnt pathway and microsatellite instability for comprehensive understanding of obstacles on the road to precision oncology in metastatic colorectal cancer.

show abstract

Treatment outcome comparisons of first‐line targeted therapy in patients with KRAS wild‐type metastatic colorectal cancer: A nationwide database study

2023

View full text Add to dashboard Cite

BackgroundThe first‐line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether bevacizumab or anti‐epidermal growth factor receptor (anti‐EGFR) monoclonal antibody (mAb) is the more effective addition to a chemotherapy doublet as the first‐line treatment for inoperable KRAS wild‐type mCRC remains controversial in prior clinical trials. Moreover, the association between the sidedness of primary tumors and the efficacy of anti‐EGFR mAb needs to be addressed.MethodsWe established a cohort of patients with KRAS wild‐type mCRC who were treated with first‐line targeted therapy plus doublet chemotherapy between 2013 and 2018 using Taiwan's National Health Insurance Research Database. Secondary surgery was defined as either resection of primary tumors, liver metastases, lung metastases, or radiofrequency ablation.ResultsA total of 6482 patients were included; bevacizumab and anti‐EGFR mAb were the first‐line targeted therapies in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Compared with those who received bevacizumab, patients who received anti‐EGFR mAb exhibited significantly longer overall survival (OS; median, 23.1 vs. 20.2 months, p = 0.012) and time to treatment failure (TTF; median, 11.3 vs. 10 months, p < 0.001). Among left‐sided primary tumors, the OS and TTF benefits of anti‐EGFR mAb remained. Among right‐sided primary tumors, the OS and TTF were similar regardless of the type of targeted therapy. In multivariate analyses, first‐line anti‐EGFR mAb therapy remained an independent predictor of longer OS and TTF for left‐sided primary tumors. Patients who received anti‐EGFR mAb were more likely to receive secondary surgery (29.6% vs. 22.6%, p < 0.0001) than patients who received bevacizumab.ConclusionFor patients who received first‐line doublet chemotherapy for KRAS wild‐type mCRC, adding anti‐EGFR mAb was associated with significantly longer OS and TTF, especially for left‐sided primary tumors.

show abstract

Relationships between tumour response and primary tumour location, and predictors of long-term survival, in patients with RAS wild-type metastatic colorectal cancer receiving first-line panitumumab therapy: retrospective analyses of the PRIME and PEAK clinical trials

Abstract: First-line panitumumab was associated with improved ETS and DpR vs. comparator in patients with left-sided mCRC. ETS may identify a subgroup of patients with right-sided disease who might respond to panitumumab.

Cited by 32 publications

References 45 publications

Relationship Between Tumor Response and Tumor-Related Symptoms in RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses From 3 Panitumumab Trials

Relationship Between Tumor Response and Tumor-Related Symptoms in RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses From 3 Panitumumab Trials

Current challenges in the implementation of precision oncology for the management of metastatic colorectal cancer

Treatment outcome comparisons of first‐line targeted therapy in patients with KRAS wild‐type metastatic colorectal cancer: A nationwide database study

Contact Info

Product

Resources

About