Dermatology-related quality-of-life outcomes in patients with RAS wild-type metastatic colorectal cancer treated with fluorouracil and folinic acid with or without panitumumab (Pmab) maintenance after FOLFOX + Pmab induction: a prespecified secondary analysis of the phase II randomized PanaMa (AIO KRK 0212) trial

Abstract

Background: The key endpoints for the assessment of the effect of maintenance therapy for metastatic colorectal cancer (mCRC) are survival and quality-of-life outcomes. We aimed to compare dermatology-related quality of life (DRQOL) in patients with RAS wild-type (wt) mCRC treated with fluorouracil and folinic acid (FU/FA) + panitumumab (Pmab) versus FU/FA alone as maintenance therapy after folinic acid, fluorouracil and oxaliplatin + Pmab induction.

Patients and methods: The phase II randomized PanaMa (AIO KRK 0212; NCT01991873) trial included 387 patients at 70 community/academic sites in Germany. For this prespecified secondary analysis, 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 second cycle of therapy until disease progression/death.

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. Patients who experienced skin toxicity according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) during induction therapy had significantly worse DRQOL according to all three measures, compared to those who did not [i.e. Skindex-16, mean difference at cycle 2 -12.87; 95% confidence interval (CI) -20.01 to -5.73; P < 0.001]. During maintenance therapy, significantly improved recovery was observed in all DRQOL measures for patients receiving FU/FA, compared to those receiving additional Pmab (i.e. Skindex-16, mean difference at cycle 6 -16.53; 95% CI -22.68 to -10.38; P < 0.001).

Conclusions: In this secondary analysis of a phase II randomized clinical trial, patient-reported DRQOL outcomes correlated with skin toxicity according to NCI-CTCAE during induction therapy. Maintenance therapy with FU/FA + Pmab was associated with deteriorated DRQOL versus FU/FA alone in patients with RAS wt mCRC.

Keywords: anti-EGFR; colorectal cancer; maintenance therapy; patient-reported outcomes; quality of life.

Figure 1

CONSORT diagram of the study population. Compliance rates (burgundy boxes), and DLQI, FACT-EGFRI and Skindex-16 questionnaire completion rates (gray boxes) are shown for the induction (top panel, olive boxes; baseline and cycle 6 of induction therapy) and maintenance (bottom panel, olive boxes; baseline and cycle 6 of maintenance therapy) population. DLQI, Dermatology Life Quality Index; FACT-EGFRI, Functional Assessment of Cancer Therapy-epidermal growth factor receptor inhibitor; FU/FA, fluorouracil and folinic acid; Pmab, panitumumab.

Figure 2

DRQOL outcomes during induction therapy. Mean changes of (A) Skindex-16, DLQI, and EGFRI scores and (B) Skindex-16 Symptom, Emotional, and Functional subdomains are shown from baseline (before start of induction therapy) for all patients (blue), patients with dermatologic toxicity (olive), and patients without dermatologic toxicity (red) at cycles 2, 4, and 6 of induction therapy. (C) Skindex-16, DLQI, and EGFRI scores and (D) Skindex-16 Symptom, Emotional, and Functional subdomains are shown from baseline (before start of induction therapy) for patients with dermatologic toxicity by CTCAE-grades 0 (red), 1 (olive), 2 (teal), and 3 (violet) at cycles 2, 4, and 6 of induction therapy. Whiskers mark 95% CI. CI, confidence interval; CTCAE, Common Terminology Criteria for Adverse Events; DLQI, Dermatology Life Quality Index; DRQOL, dermatology-related quality of life; EGFRI, epidermal growth factor receptor inhibitor.

Figure 2

DRQOL outcomes during induction therapy. Mean changes of (A) Skindex-16, DLQI, and EGFRI scores and (B) Skindex-16 Symptom, Emotional, and Functional subdomains are shown from baseline (before start of induction therapy) for all patients (blue), patients with dermatologic toxicity (olive), and patients without dermatologic toxicity (red) at cycles 2, 4, and 6 of induction therapy. (C) Skindex-16, DLQI, and EGFRI scores and (D) Skindex-16 Symptom, Emotional, and Functional subdomains are shown from baseline (before start of induction therapy) for patients with dermatologic toxicity by CTCAE-grades 0 (red), 1 (olive), 2 (teal), and 3 (violet) at cycles 2, 4, and 6 of induction therapy. Whiskers mark 95% CI. CI, confidence interval; CTCAE, Common Terminology Criteria for Adverse Events; DLQI, Dermatology Life Quality Index; DRQOL, dermatology-related quality of life; EGFRI, epidermal growth factor receptor inhibitor.

Figure 3

DRQOL outcomes during maintenance therapy. Mean changes of (A) Skindex-16, DLQI, and EGFRI scores and (B) Skindex-16 Symptom, Emotional, and Functional subdomains are shown from baseline (before start of maintenance therapy) for patients who received FU/FA plus Pmab (red) or FU/FA (blue) for every second cycle at cycles 2-16 of maintenance therapy. Whiskers mark 95% CI. CI, confidence interval; DLQI, Dermatology Life Quality Index; DRQOL, dermatology-related quality of life; EGFRI, epidermal growth factor receptor inhibitor; FU/FA, fluorouracil and folinic acid; Pmab, panitumumab.