medwireNews: Preoperative pelvic radiotherapy can be omitted in patients with locally advanced rectal cancer who respond to neoadjuvant chemotherapy, say the PROSPECT investigators.
Neoadjuvant FOLFOX with selective use of chemoradiotherapy was noninferior to chemoradiotherapy with respect to the primary endpoint of disease-free survival (DFS), reported Deborah Schrag, from the Memorial Sloan Kettering Cancer Center in New York, USA, at the 2023 ASCO Annual Meeting in Chicago, Illinois, USA.
She added that secondary outcomes, such as local recurrence rates, overall survival, and complete resection rates, were also comparable between the groups.
“Neoadjuvant FOLFOX, with only the selective use of pelvic chemoradiation, is a safe and effective treatment option for patients with clinical T2 node-positive, clinical T3 node-negative, or clinical T3 node-positive rectal cancer,” said Schrag.
Speaking to the press, she commented that given the rising number of young patients with colorectal cancer, this approach “provides an option for patients who wish to preserve fertility or avoid early menopause.”
The randomized phase 3 trial enrolled 1128 patients with locally advanced rectal cancer who were candidates for sphincter-sparing surgery. A total of 585 participants received six cycles of FOLFOX, followed directly by total mesorectal excision if restaging showed a clinical response of at least 20%, but if they had a lower response or intolerance to FOLFOX they underwent pelvic chemoradiation (5040 cGy over 5.5 weeks with either capecitabine or 5-fluorouracil) before surgery. The remaining 543 patients received pelvic chemoradiation before surgery. Patients in both groups received adjuvant chemotherapy – either FOLFOX or CAPOX at the physician’s discretion.
At a median follow-up of 58 months, the DFS rate at 5 years was 80.8% in the FOLFOX group and 78.6% in the chemoradiotherapy group. The hazard ratio for recurrence or death was a nonsignificant 0.92 and the upper limit of the two-sided 90.2% confidence interval did not exceed 1.29, thereby demonstrating the noninferiority of the FOLFOX regimen.
The presenter pointed out that “adjusting for nodal status and age did not change this result.”
The rates of local recurrence “were very low and nearly identical” in the FOLFOX and chemoradiotherapy groups, she continued, noting that the 5-year local recurrence-free rates were 98.2% and 98.4%, respectively.
Overall survival at 5 years was also similar, with rates of 89.5% among patients who received FOLFOX plus selective chemoradiation and 90.2% among those given chemoradiation.
There was no significant difference between the treatment arms with respect to surgical and pathologic endpoints either. For instance, the complete rectal resection rates were 99% with FOLFOX and 97% with chemoradiation, while the corresponding pathologic complete response rates were 22% and 24%.
During neoadjuvant therapy, adverse events (AEs) of at least grade 3 as reported by clinicians occurred in 41% of FOLFOX-treated patients and 23% of those given chemoradiation, but Schrag drew attention to the fact that “the observation period for reporting toxicity was more than twice as long in the FOLFOX group.”
And she added that the rate of clinician-reported grade 3 or worse AEs was lower in the FOLFOX treatment arm during the adjuvant period, at 25% versus 39% in the chemoradiation arm.
The PROSPECT trial also evaluated patient-reported toxicity, and this showed significantly higher incidence of several AEs in the FOLFOX versus chemoradiation groups during neoadjuvant treatment. For instance, severe fatigue occurred in 42% versus 20% of patients, while severe constipation, appetite loss, and nausea were reported by 27% versus 11%, 22% versus 9%, and 21% versus 7% of patients, respectively.
By contrast, just the incidence of severe diarrhea was higher in the chemoradiation than FOLFOX group, at rates of 20% versus 6%.
“At 12 months, patient reports of severe adverse symptoms were low, all in the single digit range, in both groups,” but the rate of severe neuropathy was significantly higher in the chemoradiation group (8 vs 3%), which the presenter attributed to a greater use of postoperative oxaliplatin.
With regard to overall health-related quality of life, there was a trend favoring FOLFOX at all timepoints, but the groups did not differ significantly. Bowel function was significantly better with FOLFOX than chemoradiation, and although sexual function was comparable during treatment, it improved significantly more after treatment among FOLFOX-treated patients, with benefits persisting at 12 and 24 months.
The efficacy results from PROSPECT are published in The New England Journal of Medicine, while the patient-reported outcomes appear in the Journal of Clinical Oncology.
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2023 ASCO Annual Meeting; Chicago, Illinois, USA: 2–6 June
N Engl J Med 2023; doi:10.1056/NEJMoa2303269
J Clin Oncol 2023; doi:10.1200/JCO.23.00903