Abstract 432P
Background
With a median age at diagnosis of around 70 years (yrs), CRC is a disease that affects many older adults. We investigated the toxicity and efficacy of adding cetux to doublet chemotherapy (DC) in older pts.
Methods
RAS WT pts receiving 1st line DC + cetux (n = 932) or DC (n = 342) from 6 mCRC trials in the ARCAD database were included. Toxicity was measured by adverse events (AE) with CTCAE grade ≥ 3 (G3+) and compared by age group (≥ 70 vs < 70 yrs). OS and PFS between DC +/- cetux in 3 randomized trials were compared using stratified Cox model, adjusting for covariates. Interaction between age and treatment groups was tested. Associations between age groups for DC + cetuximab in all 6 trials were evaluated for outcomes and toxicity by multivariable cox model and logistic regression.
Results
RAS WT pts ≥ 70 yrs (age median [range] 73 [70-89], 70% male) were more likely than pts < 70 (age median [range] 58 [19-69], 63% male) to have PS 1 (50% vs 42%; p = 0.048), right colon (42% vs 29%; p = 0.013), and lung metastasis (40% vs 30%; p = 0.005). Pts ≥ 70 (vs < 70) had no difference in G3+ AE for neutropenia/leukopenia (23% vs 22%; p = 0.84), diarrhea (14% vs 12%; p = 0.83) or nausea/vomiting (9% vs 8%; p = 0.87). When comparing DC +/- cetux, no significant difference in OS was observed within each age group. PFS improved by adding cetux in pts < 70. Interaction tests were not significant. Pts ≥ 70 (vs < 70) receiving DC + cetux had similar PFS (HRadj [95% CI] = 1.23 [0.99 – 1.5]; p = 0.063) but inferior OS (HRadj [95% CI] = 1.38 [1.1 – 1.7]; p = 0.006). Table: 432P
Comparing OS and PFS between treatments within age groups (DC +/- cetux)
| Outcome | Age < 70 | Age ≥ 70 | ||
| DC | DC + cetux | DC | DC + cetux | |
| OS* | ||||
| Events/N | 104/129 | 88/114 | 31/35 | 21/31 |
| Median (95% CI) | 17.9 (14.7 - 23.3) | 19.5 (16.5 - 23.5) | 19.4 (11.8 - 22.5) | 16.3 (12.2 - NE) |
| HRadj (95% CI) | 0.90 (0.67 - 1.21) | 1.03 (0.54 - 1.98) | ||
| P-value | 0.50 | 0.92 | ||
| P-value (Interaction) | 0.43 | |||
| PFS* | ||||
| Events/N | 108/129 | 85/115 | 33/35 | 24/31 |
| Median (95% CI) | 8.7 (7.4 - 9.7) | 9.4 (8.7 - 12.1) | 8.80 (6.9 - 9.8) | 9.00 (6.9 - 13.9) |
| HRadj (95% CI) | 0.66 (0.49 - 0.90) | 0.97 (0.52 - 1.80) | ||
| P-value | 0.008 | 0.92 | ||
| P-value (Interaction) | 0.89 |
*Adjusted for ECOG PS, sex, primary tumor location, and number and site of metastasis.
Conclusions
Pts with RAS WT mCRC ≥ 70 yrs old had comparable toxicity and similar efficacy to younger pts when cetux was added to DC and adjusting for key confounders. This is the most comprehensive analysis on the use of cetux in RAS WT older pts.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
ARCAD.
Funding
Merck KGaA.
Disclosure
D. Papamichael: Advisory/Consultancy: Roche; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Novartis; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Merck Serono; Research grant/Funding (institution): MSD. All other authors have declared no conflicts of interest.