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

Abstract

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.

Impact of early tumor shrinkage on quality of life in patients treated with first-line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: results of Phase II QUACK trial

“…This exploratory analysis used the EORTC questionnaire and found that ETS was associated with less deterioration of GHS/QOL and functioning. In a retrospective analysis of data from three trials of first-line chemotherapy plus the anti-EGFR antibody panitumumab in RAS -wild-type mCRC, the onset of new tumor-related symptoms, defined as new opiate use, weight loss, anemia, asthenia, and decline in ECOG PS, was delayed by achieving ETS, regardless of the treatment regimen received [ 36 ]. These findings suggest that HRQOL may remain relatively constant in mCRC patients with ETS.…”

“…Importantly, the objective response rate is not a reliable surrogate for PFS or OS [ 38 ]. On the other hand, ETS is defined as a minimum tumor reduction of 20% 6–8 weeks after the initiation of treatment, and it has been found to be associated with favorable prognostic outcomes in post hoc analyses in several trials, independent of the agents used and cancer types [ 16 , 18 , 28 , 29 , 31 , 36 , 37 , 39 – 46 ]. We confirmed that ETS was significantly associated with prolonged PFS, OS, and TTF.…”

Relationships Between Köhne Category/Baseline Tumor Load and Early Tumor Shrinkage, Depth of Response, and Outcomes in Metastatic Colorectal Cancer

“…15 Early characterization of response can enable key treatment decisions to be taken sooner (eg, a change of therapy for non-responders, particularly for right-side disease, or early planning of surgical intervention, particularly in candidates for liver resection), potentially leading to less exposure to systemic therapy for patients. Early and deep responses to treatment may provide patients with relief from tumor-related symptoms 40 and enable surgical resection to be performed. There are major benefits to be gained from resecting tumors earlier: resection can provide long-term, relapse-free survival or cure, while reduced long-term cancer therapy lowers the occurrence of adverse effects such as liver toxicity and complications of surgery.…”