For patients with high-risk locally advanced rectal cancer, a short course of radiotherapy followed by consolidative chemotherapy and then surgery significantly reduced the rate of treatment failure, compared with standard chemoradiotherapy, results of a randomized trial show.
according to investigator Geke A.P. Hospers, MD, PhD.
The rate of pathological complete response (pCR) nearly doubled, from about 14% for the conventional approach to about 28% for short-course (25 Gy in 5 fractions) radiotherapy then CAPOX or FOLFOX4 followed by total mesorectal excision (TME), reported Dr. Hospers, a medical oncologist and professor at University Medical Center Groningen in the Netherlands.
Three-year survival was high at about 89% in both groups, she said, with no unexpected toxicity and no differences in surgery, postoperative complications, or quality of life.
Based on these results, the short-course radiotherapy followed by chemotherapy and TME “can be considered as a new standard of care,” Dr. Hospers and coauthors concluded in their report on the RAPIDO trial, which was of part of the American Society of Clinical Oncology virtual scientific program.
In agreement was Christopher L. Hallemeier, MD, who said in a virtual ASCO discussion of the RAPIDO trial that short-course radiotherapy followed by consolidative chemotherapy “is a standard option” for many patients and is, in fact, now endorsed in National Comprehensive Cancer Network (NCCN) guidelines.
“I should point out that 5 fractions of radiotherapy is COVID-19 friendly in that it reduces the number of visits to the health care facility,” said Dr. Hallemeier, of Mayo Clinic in Rochester, Minn.
Several questions remain, however, including whether clinicians should be concerned about a trend toward a higher risk of locoregional failure seen in the RAPIDO results and why there was a lack of difference in OS.
“Could it be we’re merely delaying distant metastases versus preventing them by more consistent use of systemic therapy sooner? Longer-term follow-up will be needed to determine whether that’s the case,” he said.
In RAPIDO, a total of 920 adult patients with adenocarcinoma of the rectum and high-risk features apparent on MRI were randomized to a standard chemoradiation arm or the experimental approach.
In the standard treatment arm, patients received chemoradiotherapy (28 fractions x 1.8 Gy or 25 fractions x 2 Gy combined with capecitabine) followed by surgery about 8 weeks later, then optional adjuvant chemotherapy (CAPOX for 8 courses or FOLFOX for 12 courses) in the centers where that approach was standard.
The experimental treatment consisted of short-course radiotherapy (5 fractions x 5 Gy) followed by chemotherapy (CAPOX for 6 courses or FOLFOX for 9 courses), then surgery 2-4 weeks later.
Disease-related treatment failure, the primary endpoint of the study, was significantly lower in the experimental arm, according to Dr. Hospers. The 3-year rate of disease-related treatment failure was 23.7% for the experimental treatment and 30.4% for standard chemoradiotherapy (hazard ratio, 0.75; 95% confidence interval, 0.60-0.96; P = .019).
According to Dr. Hospers, the difference in rates of treatment failure was primarily caused by a significant decrease in distant metastases, at 20% and 26.8% in the experimental and standard treatment arms, respectively, at 3 years (P = .005).
The rate of pCR was 28.4% for the experimental arm, versus 14.3% for standard treatment (P < .001), Dr. Hospers reported.
Grade 3 or greater neurologic toxicity was more common in the experimental arm, occurring in 4.3% versus 0.2% in the standard treatment arm, which Dr. Hospers said was expected because of the administration of oxaplatin. Likewise, there was a higher percentage of grade 3 or greater thromboembolic events in the experimental group (8.5% vs. 4.1%) and more grade 3 or greater diarrhea (17.6% vs. 9.3%).
Subgroup analysis showed that the experimental approach was favored over conventional chemoradiotherapy whether or not patients in the conventional arm went on to receive the optional adjuvant chemotherapy, according to Dr. Hospers.
Results of RAPIDO have the potential to change the standard of care for locally advanced rectal cancer, according to Suneel Kamath, MD, a gastrointestinal oncologist with Cleveland Clinic in Cleveland, Ohio.
The pCR rate with short-course radiation followed by chemotherapy is “excellent,” compared with what’s typically seen with standard, long-course chemoradiation, Dr. Kamath said in an interview.
“This proves that we don’t necessarily need long-course radiation for larger tumors or larger number of lymph nodes to get good down-staging,” he said.
The lower rate of distant metastatic disease with the short-course radiation and preoperative chemotherapy arm was also notable, Dr. Kamath said.
The study was sponsored by the University Medical Center Groningen. Dr. Hospers reported institutional disclosures related to Amgen, Bristol-Myers Squibb, MSD, Novartis, Roche, and Seerave Foundation. Dr. Hallemeier reported honoraria and travel expenses from Focus Medical Communications and Imedex. Dr. Kamath had no relevant disclosures.
SOURCE: Hospers GAP et al. ASCO 2020, Abstract 4006.