Adding radiation to chemo proffers no relapse-free survival advantage in locally advanced endometrial cancer
The addition of radiation therapy to chemotherapy does not provide a relapse-free survival (RFS) advantage over chemotherapy only in stage III or IVA endometrial cancer, according to the phase III GOG 258* trial.
“The trial was supposed to be a positive trial demonstrating that the combined regimen was superior to chemotherapy given alone,” said lead investigator Professor Daniela Matei from Northwestern University Feinberg School of Medicine, Chicago, Illinois, US.
“Our results indicate the combined regimen of radiation and chemotherapy did not result in an improvement in RFS, and that chemotherapy alone remains the standard of care for stage III uterine cancer,” she said.
The study population comprised 736 adult women (median age 60 years) with stage III or IVA endometrial carcinoma** who had undergone hysterectomy and bilateral salpingo-oophorectomy within the last 8 weeks. They were randomized to receive chemoradiotherapy (cisplatin [50 mg/m2] plus tumour volume-directed external-beam radiation therapy on days 1 and 29, followed by carboplatin [area under the curve (AUC) 5–6] plus paclitaxel [175 mg/m2]; n=346) every 21 days for four cycles or chemotherapy only (carboplatin [AUC 6] plus paclitaxel [175 mg/m2]) every 21 days for six cycles (n=361). Only patients with adnexal, lymph node, and pelvic, nonperitoneal metastasis were included. They were followed up for a median 47 months.
At 5 years, the RFS rate did not differ between chemoradiotherapy and chemotherapy-only recipients (59 percent vs 58 percent, hazard ratio [HR], 0.90, 90 percent confidence interval [CI], 0.74–1.10; p=0.20). [N Engl J Med 2019;380:2317-2326]
At 5 years, distant recurrence occurred more frequently in chemoradiotherapy compared with chemotherapy-only recipients (27 percent vs 21 percent, HR, 1.36, 95 percent CI, 1.00–1.86). However, vaginal recurrence at 5 years was less common in chemoradiotherapy vs chemotherapy-only recipients (2 percent vs 7 percent, HR, 0.36, 95 percent CI, 0.16–0.82), as was pelvic and para-aortic lymph node recurrence (11 percent vs 20 percent, HR, 0.43, 95 percent CI, 0.28–0.66).
“For patients at high risk of a local relapse, radiation may be occasionally necessary to prevent pelvic recurrences,” said Matei.
Grade 3–5 adverse events (AEs) occurred in 58 and 63 percent of women in the chemoradiotherapy and chemotherapy-only arms, respectively. The two treatment-related deaths (one incident each of grade 5 sepsis and sudden death) occurred in the chemotherapy-only arm. AEs of any grade that occurred more frequently in the chemoradiotherapy vs chemotherapy-only arms included constitutional symptoms, fatigue, and gastrointestinal, renal/genitourinary, and musculoskeletal events, while haematologic AEs were common and severe in chemotherapy-only recipients.
Quality of life assessments pointed to worse gastrointestinal symptoms at weeks 6 and 18 among chemoradiotherapy vs chemotherapy-only recipients, while neurotoxicity symptoms were worse in chemotherapy-only recipients at 6 weeks.
According to the researchers, the administration of pelvic or whole abdominal radiation therapy following surgery is effective in preventing local recurrence, but less so for systemic recurrence. “Chemotherapy became the mainstay of treatment for high-risk endometrial carcinoma after it became clear that distant metastasis is a key determinant of survival in patients with locally advanced endometrial carcinoma,” they said.
They also noted the higher rate of chemotherapy treatment completion among chemotherapy-only vs chemoradiotherapy recipients (85 percent vs 75 percent).
“[C]oncomitant delivery of chemo and radiotherapy can result in decreased tolerance of the treatment and incomplete delivery of chemotherapy,” said Matei. “Our data are compatible with findings from prior studies that the completion of chemotherapy is key to preventing distant relapse,” she added.