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 Dec;18(4):245-256.e5. doi: 10.1016/j.clcc.2019.07.009. Epub 2019 Jul 29.


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 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 wild-type mCRC patients. Treatments with high cytoreductive potential may delay symptom development.

Keywords: Anemia; Asthenia; Early tumor shrinkage; Opiate use; Weight loss.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Humans
  • Leucovorin / administration & dosage
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mutation*
  • Organoplatinum Compounds / administration & dosage
  • Panitumumab / administration & dosage
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Young Adult
  • ras Proteins / genetics*


  • Organoplatinum Compounds
  • Panitumumab
  • ras Proteins
  • Leucovorin
  • Fluorouracil

Associated data