Early Cytoreductive Treatment Delays Onset of Symptoms Associated with Metastatic Colorectal Carcinoma

Symptoms Associated with Cancer

Advanced cancer is often associated with the occurrence of unpleasant symptoms such as pain, loss of appetite, fatigue, and asthenia. According to current recommendations, therapy for patients with severe symptoms should be intensive in order to prevent rapid deterioration and to prolong patient survival. However, there is currently no standardized method for assessing symptoms, so it is up to the treating physician to determine which symptoms are relevant for a particular patient.

The presented analysis examined data from 3 clinical trials of panitumumab in the first-line treatment of mCRC. The authors evaluated whether early tumor shrinkage (ETS) and depth of response (DpR) correlated with the time to the occurrence of symptoms associated with the tumor.

Analysis Methodology and Patient Population

A total of 659 patients who received panitumumab in combination with chemotherapy were included in the analysis from the PRIME, PEAK, and Study 314 clinical trials. All patients were treated in the first line, and only those with no mutations in the RAS gene (wt RAS) for whom ETS could be evaluated were included in the analysis.

Achieving ETS was defined as a reduction of at least 30% in the sum of the longest diameters of lesions by week 8 of treatment. DpR was calculated as the maximum percentage change in tumor size from baseline. The number of patients who developed the following tumor-associated symptoms during the clinical trials was determined: the need for opioid analgesics, a weight loss of at least 10% from baseline, the occurrence of anemia, or asthenia. The composite endpoint assessed was the occurrence of any of the described symptoms.

Results

ETS ≥ 30% was achieved by 329 patients. Basic demographic characteristics and disease course did not differ significantly across the three studies between patients who achieved ETS ≥ 30% and those with ETS < 30%. The onset of new tumor-associated symptoms was delayed in patients with ETS ≥ 30% (median 5.0 months) compared to patients with ETS < 30% (median 3.4 months; hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.66–0.97; p = 0.0213). A greater DpR was also associated with a delay in symptom onset, particularly among patients who were asymptomatic at study entry.

The presence of symptoms at study entry was associated with a shorter median overall survival (21.2 vs. 27.8 months in asymptomatic patients; HR 1.30; 95% CI 1.08–1.56; p = 0.0054). However, the overall survival of patients who achieved ETS ≥ 30% was comparable regardless of the occurrence of tumor-associated symptoms at study entry (31.7 months in symptomatic vs. 36.4 months in asymptomatic patients; HR 1.10; 95% CI 0.80–1.49; p = 0.5671).

Conclusion

Early tumor shrinkage and depth of response were associated with a delay in the onset of tumor-associated symptoms in mCRC patients with non-mutated RAS oncogene. Treatment with high cytoreductive potential, such as the combination of panitumumab with chemotherapy, can delay the onset of symptoms associated with advanced cancer.

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Source: Taieb J., Geissler M., Rivera F. et al. Relationship between tumor response and tumor-related symptoms in ras wild-type metastatic colorectal cancer: retrospective analyses from 3 panitumumab trials. Clin Colorectal Cancer 2019; 18 (4): 245–256.e5, doi: 10.1016/j.clcc.2019.07.009.