Neoadjuvant chemotherapy potential alternative to neoadjuvant chemoradiotherapy in LARC

Results from the phase 3, open label CONVERT study suggest neoadjuvant chemotherapy to be non-inferior to neoadjuvant chemoradiation in patients with locally advanced rectal cancer (LARC).

Combined chemoradiation therapy is currently the standard practice for LARC with uninvolved mesorectal fascia. Results from the FOWARC trial were promising for neoadjuvant chemotherapy, but this trial (n=165 patients/arm) was not powered for non-inferiority [1]. The CONVERT study (NCT02288195) was conducted to compare neoadjuvant chemotherapy (capecitabine, oxaliplatin) with standard chemoradiotherapy with capecitabine for these patients. Dr Pei-Rong Ding (Sun Yat-sen University Cancer Center, China) presented the first results [2].

A total of 663 patients with LARC within 12 cm from the anal verge and uninvolved mesorectal fascia were 1:1 assigned to receive 4 cycles of chemotherapy alone (nCT arm) or chemoradiotherapy with concurrent capecitabine (nCRT arm). After surgery, patients in the nCT arm were treated with 4 additional cycles of capecitabine/oxaliplatin, whereas patients in the nCRT arm were treated with 6 additional cycles of capecitabine/oxaliplatin. Primary endpoint of the CONVERT study was 3-year locoregional failure-free survival.

Of 589 patients who started neoadjuvant treatment, 86.3% of patients accomplished full dose of neoadjuvant therapy in the nCT arm compared with 91.0% in the nCRT arm (P=0.074). Of all patients who received adjuvant chemotherapy (n=457), 52.8% of patients accomplished full dose of adjuvant chemotherapy in the nCT arm compared with 44.1% in the nCRT arm (P=0.065).

The pathologic complete response (pCR) rate was 11.0% in the nCT arm versus 13.8% in the nCT arm (P=0.333). Good downstaging (ypStage 0 to 1) rate was 40.8% versus 45.6% (P=0.265). nCT significantly reduced perioperative distant metastases compared with nCRT (0.7% vs 3.1%; P=0.034; see Figure). Two patients in the nCT arm and 5 patients in the nCRT arm achieved complete clinical response and were treated with a non-operative approach. Fewer preventive ileostomies were observed in nCT arm (52.2% vs 63.6%; P=0.008). Both arms had similar short-term toxicity and postoperative complications, although nCT appeared more toxic (12.3% vs 8.3% of grade 3–4 adverse events). Similar results were observed in subgroup analysis.

Figure: Surgical and pathological results of CONVERT [2]



“nCT achieved similar pCR and good downstaging rate with less peri-operative distance metastasis and preventive colostomy compared with nCRT,” concluded Dr Ding. However, pCR, cCR, and downstaging were numerically better for nCRT and nCT remained slightly more toxic. “Long-term follow-up, especially data on disease-free survival and overall survival, is needed to confirm these results.”

1. Deng Y, et al. J Clin Oncol. 2019;37: 3223-3323.
2. Ding P-R, et al. Neoadjuvant chemotherapy with oxaliplatin and capecitabine versus chemoradiation with capecitabine for locally advanced rectal cancer with uninvolved mesorectal fascia (CONVERT): Initial results of a multicenter randomised, open-label, phase III trial. Abstract LBA22, ESMO Congress 2021, 16–21 September.

 

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Posted on 19 November, 202128 March, 2024