Dermatology-related quality of life outcomes in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC) treated with fluorouracil and folinic acid with or without panitumumab (Pmab) maintenance after FOLFOX + Pmab induction: A prespecified secondary analysis of the phase 2 randomized PanaMa (AIO KRK 0212) trial.
Authors: Ballhausen Alexej , Karthaus Meinolf , Fruehauf Stefan , Graeven Ullrich , Müller Lothar , Koenig Alexander , Von Weikersthal Ludwig Fischer , Sommerhäuser Greta , Jelas Ivan , Alig Annabel Helga Sophie , Kurreck Annika , Stahler Arndt , Goekkurt Eray , Held Swantje , Kasper Stefan , Heinrich Kathrin , Heinemann Volker , Stintzing Sebastian , Trarbach Tanja , Modest Dominik Paul 
Published: June 2024

e15539

Background: The addition of anti-EGFR antibodies (i.e. Pmab) to maintenance therapy has demonstrated improved progression-free survival (PFS) in patients with RAS wt mCRC, with no impact on health related quality of life (HRQOL) measured by EORTC-QLQ-C30. Here, we report the specifically assessed dermatology-related quality of life (DRQOL) from the PanaMa trial (AIO KRK0212). Methods: DRQOL outcomes were assessed using the Functional Assessment of Cancer Therapy- Epidermal Growth Factor Receptor Inhibitor (FACT-EGFRI), Dermatology Life Quality Index (DLQI), and Skindex-16 questionnaires at every cycle of therapy until disease progression/death. DRQOL outcomes were mean changes in DRQOL scores from baseline (prior to cycle 1 of therapy) to every second cycle of treatment (both induction and maintenance therapy). Multiple linear regression analyses was used to test for impact of baseline characteristics and toxicity endpoints on DRQOL outcomes. Results: At least one DRQOL questionnaire was completed by a total of 310/377 (82%) patients who received induction therapy, and by 216/248 (87%) patients who were randomized and received maintenance therapy. During induction therapy, significant deterioration was observed in all DRQOL measures, most prominently for mean Skindex-16 scores (mean deterioration 26.78; 95% CI 23.24—30.32; P < 0.001). Between cycles 1 and 6 of maintenance therapy, patients receiving FU/FA had significant recovery in all DRQOL measures (i.e. Skindex-16, mean difference -23.26; 95% CI -29.37—17.15; P < 0.001), while those receiving additional Pmab did not. At cycle 6 of maintenance, patients who received FU/FA + Pmab maintenance had significantly worse mean DRQOL scores, compared to those who received FU/FA alone (Skindex-16, mean difference -16.53; 95% CI -22.68—10.38; P < 0.001). Multiple linear regression including baseline characteristics and toxicity endpoints significantly predicted all DRQOL measures, i.e. Skindex-16 scores at cycle 6 of maintenance (F [18, 105] = 3.23, R2 = 0.36, P < 0.001). Strongest individual predictors for favorable Skindex-16 outcomes were FU/FA arm (t = -5.49, P < 0.001) and ECOG 0 (t = -3.08, P = 0.003). Conclusions: Patients randomized to maintenance treatment with FU/FA + Pmab reported a significant disadvantage in terms of DRQOL outcomes according to multiple validated measures as compared to patients receiving FU/FA alone. These results suggest that patient reported outcomes by FACT-EGFRI, DLQI, and Skindex-16 reflect toxicity as recorded by classic toxicity scores which are not covered by global HRQOL assessment. These data, together with HRQOL may support clinical decision-making of maintenance therapy. Clinical trial information: NCT01991873 .