Differences in clinician and patient assessment of baseline neuropathy in patients receiving taxane-based chemotherapy enrolled to SWOG S1714 (NCT# 03939481).
Authors: Trivedi Meghna S. , Unger Joseph M. , Hershman Dawn L. , Darke Amy , Hertz Daniel Louis , Brannagan Thomas , Smith Stephanie , Irvin William Johnson , Hathaway Amanda Redden , Vander Woude Amy C. , Gudena Vinay K. , Henry Norah Lynn , Fisch Michael Jordan 
Published: June 2022

12024 Background: Chemotherapy induced peripheral neuropathy (CIPN) can lead to treatment dose reduction or discontinuation and significantly impact quality of life and functional status. Clinical trials have historically excluded patients with pre-existing neuropathy. Thus, it is unknown how many patients start treatment with baseline neuropathy as well as the impact on the trajectory of neuropathy symptoms. There are several patient- and clinician-based methods to assess CIPN; however, there is no consensus on the best method to evaluate CIPN or whether clinician versus patient assessment differs at baseline. Methods: In SWOG 1714, we enrolled patients ≥ 18 years of age with Stage I-III non-small cell lung, breast, or ovarian/fallopian tube/peritoneal cancer starting treatment with a taxane. Patients with baseline neuropathy were eligible. Neuropathy was assessed with patient-reported outcomes (PROs), including the European Organization for Research and Treatment of Cancer QLQ-CIPN20 (CIPN-20) and the PRO version of the Common Terminology criteria for Adverse Events (PRO-CTCAE) for severity of and interference caused by numbness and tingling, and the clinician-assessed National Cancer Institute (NCI)-CTCAE Grading Scale Version 5.0 for nervous system disorders. Results: Of 1336 patients enrolled on S1714, 1322 (99.0%) were eligible. The median age was 55.7 years (range 23.9-85.5) and 98.9% were female. The cohort was racially/ethnically diverse with 73.6% White, 11.3% Black, 4.6% Asian, and 10.5% Other and 10.5% Hispanic/Latino. Most of the patients enrolled had breast cancer (91%) and 67 patients (5.1%) reported having a neurological condition. Paclitaxel was administered to 60.2% and docetaxel to 39.8% and 98.5% planned to start treatment with full dose of taxane. Based on clinician assessment with NCI-CTCAE, 87.6% of patients at baseline had Grade 0 peripheral sensory neuropathy, 10.2% Grade 1, 2.0% Grade 2, and 0.2% Grade 3. The mean baseline CIPN-20 sensory subscore (range 0-100, higher number indicating greater severity) was 5.68 (standard deviation 10.41). Using the PRO-CTCAE for severity of numbness and tingling, 75.4% reported no baseline symptoms, 18.2% "mild", 4.8% "moderate", 1.1% "severe", and 0.5% "very severe" symptoms. With respect to interference of numbness and tingling with daily activities, 88.5% reported “not at all”, 8.3% “a little bit”, 2.0% “somewhat”, 0.9% “quite a bit”, and 0.3% “very much”. Conclusions: In this diverse cohort of predominantly breast cancer patients, there was limited evidence of significant pre-existing neuropathy. Clinician assessments of neuropathy may underestimate the symptoms of patients, emphasizing the importance of PROs in evaluating symptoms, particularly when baseline symptom is an exclusion criterion for clinical trials. Funding: NIH/NCI/NCORP grant UG1CA189974