Adding cisplatin to radiation fails to extend survival in intermediate-risk cervical cancer
Key takeaways:
- Chemoradiation and radiation alone conferred comparable RFS and OS benefits.
- Grade 3/grade 4 adverse events occurred more frequently among women assigned chemoradiation.
The addition of concurrent cisplatin to adjuvant radiation therapy conferred no benefit to women with intermediate-risk, early-stage cervical cancer who underwent radical hysterectomy, according to randomized phase 3 study results.
Women assigned chemoradiation achieved comparable RFS and OS as those assigned radiation alone, findings presented at Society of Gynecologic Oncology Annual Meeting on Women’s Cancer showed.
The cisplatin regimen also appeared associated with significantly more grade 3/grade 4 toxicity.
Chemoradiation is standard therapy for cervical cancer, both in the primary setting and in the adjuvant setting after radical hysterectomy.
The decision to add chemotherapy to adjuvant radiation often is based on presence of risk factors such as parametrial invasion, positive lymph nodes or resection margin.
No evidence exists to support a survival benefit with chemoradiation for patients with intermediate-risk disease, according to Sang Young Ryu, MD, of Korea Cancer Center Hospital in South Korea.
The randomized GOG 92 trial showed improved outcomes with adjuvant radiation vs. no further treatment for women with intermediate-risk disease.
“Our question was very simple and classic: Why not chemoradiation for these patients?” said Ryu, noting some retrospective studies yielded results that favored radiation but other research showed no benefit.
The NRG Oncology/GOG-263 trial included 340 women with stage I to stage IIA cervical cancer who underwent radical hysterectomy plus bilateral pelvic lymph node dissection and had at least two intermediate-risk factors.
Researchers assigned 172 women to radiation alone. They assigned the other 168 to concurrent cisplatin dosed at 40 mg/m2 weekly. Women in both groups could receive intensity-modulated radiation therapy (IMRT).
The efficacy analysis included 158 patients (median age, 46.5 years; range, 28-88; 50% Asian) assigned radiation alone and 158 patients (median age, 45 years; range, 25-78; 55.1% Asian) assigned chemoradiation. The groups appeared balanced for performance status, histology, tumor grade and other clinical factors.
RFS served as the primary endpoint. OS, adverse events and quality of life served as secondary endpoints.
A lower percentage of women assigned chemoradiation than radiation alone completed 28 fractions of radiation (87.3% vs. 97.5%) or achieved a total dose of at least 50.4 Gy (87.3% vs. 97.5%). However, radiation compliance did not differ significantly between groups.
Results showed no significant difference in 3-year RFS (88.5% vs. 85.4%; HR = 0.69; 95% CI, 0.4-1.19) or OS (97.2% vs. 90.3%; HR = 0.58; 95% CI, 0.28-1.19) between the chemoradiation and radiation-only groups.
Subgroup analyses revealed a potential favorable role for IMRT vs. X-ray radiation therapy.
Ryu called this finding “interesting” despite the difference not reaching statistical significance.
“We don’t know why there is some favorable interaction with survival outcomes,” Ryu said. “Future clinical trials are needed to investigate the role of IMRT.”
Grade 3/grade 4 adverse events occurred more frequently in the chemoradiation group, including blood or lymphatic events such as anemia or febrile neutropenia (6.2% vs. 0.6%) or gastrointestinal events such as diarrhea or nausea (7.5% vs. 5.9%). More cases of grade 3/grade 4 neutropenia (n = 27 vs. 2), leukopenia (n = 45 vs. 3) and thrombocytopenia (n = 4 vs. 0) occurred in the chemoradiation group.
Selection criteria may have affected the results, Ryu said, noting inclusion of patients with higher risk may be more likely to derive benefit from chemoradiation.
Perspective
Back to TopThere have been many retrospective reports evaluating the benefit of radiation vs. cisplatin with concurrent radiation for patients with intermediate-risk criteria.
In GOG-263, Ryu and colleagues prospectively evaluated this clinical question, and approximately 85% of patients could compete six cycles of cisplatin with concurrent chemoradiation. There also was a statistically significant difference in the number of radiation fractions, the total radiation dose and radiation duration of therapy, which we know are critical to our patients, to the detriment with use of concurrent chemotherapy.
Rates of 3-year recurrence-free survival and overall survival did not differ significantly.
During this trial, which lasted from April 2010 until April 2022, there was supposed to be 534 accrued patients. Ultimately, due to low accrual, we had only 315 patients accrue. This was a 12-year timeframe, with several key changes in cervical cancer occurring during that time.
First, it was determined by the LACC trial that minimally invasive radical hysterectomy had an associated lower rate of disease-free survival compared with open radical hysterectomy for women with stage IA to IB disease. The trial accrual from June 2008 to 2017 overlapped with GOG-263.
Additionally, the allowance of IMRT was at the discretion of the radiation oncologist. Therefore, there were very low numbers of patients who actually received IMRT, which may have further improved the tolerability of the concurrent chemotherapy.
We know health-related quality outcomes have been increasingly recognized as a critical metric for quality care. Various studies have shown [collection of] patient-reported outcomes improves survival, and that quality of life extends the cancer treatment tolerability period, detects recurrence and results in lower hospitalization rates for our patients.
The GOG 263 team utilized several validated quality-of-life measures and had comparable survey completion rates in both groups at each time point. During the first 3 and 7 weeks of treatment, there were significant decrements in quality of ife in both groups, but these equalized at 36 weeks. There was no difference in neuropathy, gastrointestinal, pain or genitourinary symptoms at 36 weeks, and they recovered to pretreatment levels, which is great.
However, the authors did not specifically use quality of life measure that would have evaluated sexuality, which would have been very informative.
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Ryu SY, et al. Randomized phase 3 trial of adjuvant radiation vs. chemoradiation in intermediate-risk, early-stage cervical carcinoma following radical hysterectomy and lymphadenectomy (results of NRG Oncology/GOG-263). Presented at: SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle.