Effect of pathohistologic complete remission (pCR) rate on the prediction of long-term prognosis following chemoradiotherapy (XRT) with cetuximab (Cet), capecitabine (CAP), and oxaliplatin (OX; Cet-CAPOX) in patients (pts) with locally advanced rectal cancer (LARC).

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e14035 Background: Preoperative XRT with Cet, CAP and OX (Cet-CAPOX) simultaneously to 50.4 Gy in fractions of 1.8 Gy has shown to be feasible, with no unexpected acute toxicity or increased perioperative morbidity, in LARC (Rödel et al., Int J Radiat Oncol Biol Phys., 2008). However, this regimen failed to show an increase in pathohistological response, incl. pCR rate, compared to reported data of 5-FU based XRT. Here, long-term results are reported. Methods: 58 pts with LARC were included in the phase I/II trial, with 40 pts evaluable for long-term efficacy (phase II). Pts characteristics: median age 63 (37-83) yrs, ECOG PS 0/1 80%/20%, at pre-therapeutic staging: cT2/3/4 3%/85%/12%, cN0/+ 20%/80%. Results: Following XRT, quality assessed TME surgery was done in all pts: low anterior resection in 70%, APR in 23%, Hartmann`s procedure in 7%. Histopathologically confirmed R0 rate was 95%. Pathology reports: ypT0N0 10%, ypT1-2N0 30%, ypT1-2N+ 5%, ypT3-4N0 25%, ypT3-4N+ 30%. Pathological tumor regression grading (TRG) according to Dworak et al.: TRG 4 (pCR) 10%, TRG 3 (>50% of tumor mass eradicated) 40%, TRG 2 (25-50%) 30%, TRG 0/1 20%. Adjuvant chemotherapy (not protocol defined) was given in 70%: 5FU/FA or CAP alone 30%, with OX 40%. With a median follow-up of 40 (3-49) months, 8 of 40 pts. (20%) have died: 1 with local R2 status and occult peritoneal metastases at staging died 5 weeks after surgery due to peritoneal tumor progression. No further locoregional failure occurred in 39 pts up to now. 3 pts. (8%) died unrelated to the malignant disease. 4 pts. (10%) developed distant metastases (liver: 1; lung: 1, both: 1, peritoneum: 1). Disease-free survival at 4 years was 77%. Conclusions: Notwithstanding the limited number of pts and follow-up time, the disappointingly poor results in terms of pathohistological response (incl. pCR) did not translate into poor long-term results. Taken into account the results of the EXPERT-C trial (Dewdney et al., ASCO GI 2011), pCR and TRG are likely insufficient parameters to assess the benefit of a cetuximab-containing perioperative XRT regimen.