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Adjuvant chemotherapy may improve gastroesophageal cancer survival
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Patients with locally advanced gastroesophageal adenocarcinoma treated with preoperative chemoradiotherapy and resection lived an average of 6 months longer when given adjuvant chemotherapy compared with observation, according to results of a retrospective study published in JAMA Oncology.
“Currently, there [are] no data which guide the use of additional chemotherapy after chemoradiation and surgery in patients with gastroesophageal cancer,” Matthew R. Porembka, MD, assistant professor of surgical oncology at UT Southwestern Medical Center and chief of surgical oncology at Parkland Hospital and Health System, told HemOnc Today. “Chemoradiation protocols often administer less systemic chemotherapy, possibly increasing the risk [for] developing recurrence. The use of adjuvant therapy has been selective, most often being offered to patients who were believed to possess a higher risk [for] recurrence.”
Limited institutional studies have shown a modest survival benefit from the use of adjuvant therapy in patients with residual disease.
Porembka and colleagues used the National Cancer Data Base to identify 10,086 adults (88% men; mean age, 61 years) diagnosis with clinical stage T1N1-3M0 or T2-4N0-3M0 adenocarcinoma of the distal esophagus or gastric cardia between 2006 and 2013.
Of those patients, 9,272 received postoperative observation and 814 underwent adjuvant chemotherapy. Patients in the chemotherapy arm were younger than those under observation (aged 18-54 years, 31% vs. 21%); were more likely to have advanced disease (ypT3/4, 62% vs. 46%; ypN+, 72% vs. 39%); and have shorter postoperative inpatient stays (longer than 2 weeks, 13% vs. 20%; P < .001 for all).
Researchers used propensity score matching to pair 732 patients in the adjuvant therapy group with 3,660 patients in the observation group.
Median follow-up of the entire matched cohort was 27 months.
OS served as the primary endpoint.
median OS compared with postoperative observation (40 months vs. 34 months; HR = 0.79; 95% CI, 0.72-0.88). A greater proportion of patients assigned adjuvant chemotherapy achieved OS at 1 year (98% vs. 88%), 3 years (54% vs. 47%) and 5 years (38% vs. 34%).
“This benefit was observed in nearly all patient subgroups,” Porembka told HemOnc Today.
Because of its retrospective design, the study did not assess adverse events associated with adjuvant chemotherapy and lacked detailed information on variables such as chemotherapy regimens.
“Given this is a retrospective study, the ability to draw definitive conclusions is limited and additional prospective trials are needed to confirm the results,” Porembka said. “In addition, future studies that help us to better understand an individual patient’s recurrence risk will be useful in tailoring the use of adjuvant therapy.”
Although the preoperative chemotherapy regimens, as well as dosage and fractionation of radiotherapy were unknown, the results demonstrated a small but potentially clinically relevant absolute OS benefit that warrants further study, Elizabeth C. Smyth, MB, BCh, MSc, and David Cunningham, MD, FMedSci, both from the department of gastrointestinal oncology and lymphoma at Royal Marsden Hospital in London, wrote in an accompanying editorial.
“Because optimal systemic chemotherapy is clearly an effective treatment for patients with resectable gastroesophageal adenocarcinoma, we think that randomization to a control arm with no active treatment following neoadjuvant chemoradiotherapy and surgery might be difficult to accept,” Smyth and Cunningham wrote. “Furthermore, given the challenge associated with administration of adjuvant chemotherapy following esophagogastrectomy, intensification of systemic treatment before chemoradiotherapy plus surgery may be more appropriate.”
This approach is under examination in the international, randomized TOPGEAR clinical trial, Smyth and Cunningham noted. – by Chuck Gormley
For more information:
Matthew R. Porembka, MD, can be reached at Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Texas 75390; email: matthew.porembka@utsouthwestern.edu.
Disclosures: The authors report no relevant financial disclosures. Smyth reports advisory roles with Bristol-Myers Squibb, Five Prime Therapeutics and Gritstone Oncology. Cunningham reports research funding from Amgen, AstraZeneca, Bayer, Celgene, MedImmune, Merck Serono, Merrimack and Sanofi.
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