Preoperative chemoradiotherapy does not improve outcomes in resectable gastric cancer
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Key takeaways:
- Preoperative chemoradiotherapy did not improve survival for individuals with resectable gastric cancer.
- The regimen did produce higher rates of complete response and tumor downstaging.
The addition of preoperative chemoradiotherapy to standard perioperative chemotherapy did not improve survival for certain patients with resectable gastric cancer, according to results of a randomized phase 3 trial.
Trevor Leong, MBBS, MD, FRANZCR, professor and consultant radiation oncologist at Peter MacCallum Cancer Centre in Australia, described the results as “somewhat surprising” and “a little disappointing” considering participants who received preoperative chemoradiotherapy had higher complete response rates and more tumor downstaging.
“We now know that with high-quality surgery and perioperative chemotherapy, preoperative chemoradiotherapy should not be used in management of patients with resectable gastric and gastroesophageal junction cancers,” Leong told Healio.
“The results will be practice changing as some centers, particularly in the U.S., currently employ preoperative chemoradiotherapy as standard treatment for gastric cancer. [That] has also been the standard of care in Europe, Canada and Australia for patients with gastroesophageal junction cancers, who comprised one-third of the [trial cohort]. National and international guideline committees will need to reconsider the current role of chemoradiotherapy in this setting.”
Background and methods
Gastric cancer is the fifth leading cause of cancer incidence and mortality around the world, according to study background.
Perioperative chemotherapy and surgery have become the standard of care for localized gastric cancer in many western countries, including the U.S.
“There is keen interest in preoperative chemoradiotherapy, which has been adopted by some centers,” Leong said. “However, comparison with perioperative chemotherapy is lacking. The role of radiation therapy in the management of resectable gastric and gastroesophageal junction cancer has been a topic of debate for more than 20 years.”
Researchers enrolled 574 adults (63% aged 50-70 years; 73% men) from 10 countries into the TOPGEAR trial. Trial participants had to have resectable adenocarcinoma of the stomach or gastroesophageal junction.
Investigators randomly assigned patients to receive preoperative chemoradiotherapy plus perioperative chemotherapy or a control regimen of perioperative chemotherapy alone.
OS served as the primary endpoint. PFS, pathologic complete response, toxicities and quality of life served as secondary endpoints.
Results and next steps
Overall, 84% of patients in the preoperative cohort and 89% from the control cohort advanced to surgery.
A higher percentage of trial participants who received preoperative therapy achieved complete response (17% vs. 8%; difference, 9%; 95% CI, 2-15).
The preoperative group also had higher rates of major pathologic response (50% vs. 29%) and tumor downstaging (32% vs. 25%).
However, the mortality rates in the preoperative group and control group appeared similar at median follow-up of 67 months (53% vs. 52%).
Researchers reported comparable median OS (46 months vs. 49 months; HR = 1.05; 95% CI, 0.83-1.31), PFS (31 months vs. 32 months; HR = 0.98; 95% CI, 0.79-1.22) and 3-year PFS (47% vs. 48%) in the preoperative and control groups. Forty percent of patients in each group remained progression free at 5 years.
Researchers reported higher rates of grade 3 or worse adverse events (66% vs. 61%), gastrointestinal toxicities (28% vs. 25%) and hematologic adverse events (46% vs. 41%) in the preoperative cohort.
Researchers acknowledged study limitations, including underrepresentation of nonwhite patients based on the U.S. population. They also cited use of different perioperative chemotherapy regimens, “which may have limited the conclusions in each chemotherapy subgroup examined separately,” they wrote.
“The doubling of pathologic complete response rates and the absence of incremental moderate to severe toxicities when chemoradiotherapy was used provide important data to guide the future exploration of radiation therapy in the management of gastric and gastroesophageal junction cancers — for example, in development of nonoperative management strategies,” Leong said.
For more information:
Trevor Leong, MBBS, MD, FRANZCR, can be reached at trevor.leong@petermac.org.
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