Preoperative chemoradiotherapy extends survival in esophagogastric junction adenocarcinoma

CHICAGO — Preoperative chemoradiotherapy conferred better survival outcomes than chemotherapy alone among patients with locally advanced esophagogastric junction adenocarcinoma, according to results of the phase 3 POET trial presented at the ASCO Annual Meeting.

Perspective from Theodore S. Hong, MD

“Results with chemotherapy alone are not sufficient. We should be able to improve [on them], and chemoradiation is one of the ways we can do that,” Michael Stahl, MD, director of the department of medical oncology at Kliniken Essen-Mitte in Germany, told HemOnc Today.

Phase 3 trial results published in 2009 showed the addition of preoperative radiotherapy to chemotherapy for patients with locally advanced esophagogastric junction adenocarcinoma increased 3-year survival from 28% to 48%; however, this result did not reach statistical significance.

The POET study included 119 patients with locally advanced disease who were randomly assigned to preoperative chemotherapy (n = 59) or chemoradiotherapy (n = 60). Rates of R0 resection were comparable between treatment groups (68% vs. 72%).

Median follow-up was 10.5 years.

Results revealed a trend toward improved 5-year survival in the chemoradiotherapy group (39.5% vs. 24.4%; HR = 0.65; 95% CI, 0.42-1.01).

Researchers also reported a significant improvement in local PFS after complete resection (HR = 0.42; 95% CI, 0.19-0.93) and improved DFS after complete resection (HR = 0.61; 95% CI, 0.36-1.01) among patients assigned chemoradiotherapy.

“The biggest implication is that we improved local control. By that, we improve long-term survival, and this is really long-term data,” Stahl said.

Results showed significant survival differences by treatment assignment among patients with Siewert type I or type II cancers; however, patients with type II cancer appeared to derive more benefit (HR for type I = 0.71; HR for type II = 0.6).

Stahl and colleagues intend to conduct a confirmatory trial in hopes of establishing preoperative chemoradiotherapy as a standard treatment.

“Another important step would be if we can predict which patients may [benefit most] from immunotherapy,” Stahl added. “It would be very nice to use immunotherapy in the adjuvant setting instead of chemotherapy.” – by Kristie L. Kahl

Reference: Stahl M, et al. Abstract 4031. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclosures: Stahl reports honoraria from Celgene, Merck Serono, Roche Pharma AG and Sanofi; consultant roles with Baxalta and Merck Sharp & Dohme; and travel, accommodations or expenses from Amgen.

Perspective

Theodore S. Hong, MD

The POET trial was a previously reported trial that evaluated the use of chemotherapy vs. chemoradiation in patients with esophagogastric junction adenocarcinoma. At the time of publication, it did not show a statistically significant improvement in OS, but a stronger trend was noted in favor of chemoradiation. Even back then, we realized that this was a very important trial because of the changing epidemiology of both gastrointestinal and esophageal cancer, with a rise in tumors that exist at the esophagogastric junction. Historically, these tumors have been included in both gastric cancer and esophageal cancer trials, typically making up about 20% to 25% of the patients included in either of these trial types. This was the first major attempt to specifically evaluate this entity of esophagogastric junction cancer to determine an optimal treatment strategy.

The long-term updates of this study confirm what the initial findings were, which show that there is a strong trend toward improved OS with the addition of radiotherapy. The improved 5-year OS was from 24.4% to 39.4%. This just missed statistical significance, likely due to the fact that the study did not complete accrual — there were only 119 patients who were randomly assigned a treatment arm.

Interestingly though, when researchers looked at RFS after complete resection, there was a statistically significant advantage to chemoradiation, with a P value of .03. The researchers appropriately recognized that, being an underpowered study, it would be nice to get additional confirmation in a definitive phase 3 trial.

I question whether this will be feasible given the CROSS trial, conducted in the Netherlands, showed a clear benefit in favor of neoadjuvant chemoradiation for esophageal cancer. Based upon the current POET trial plus the CROSS trial, many physicians are choosing preoperative chemoradiation as opposed to preoperative chemotherapy. It is not to say that it is incorrect to start with chemotherapy, but the growing trend based upon the suggested results of these studies seems to favor moving forward with chemoradiation, which most providers have a high level of comfort with at this time.

I would urge physicians not to consider going to surgery first for a locally advanced esophagogastric junction adenocarcinoma, whereby one would have to consider postoperative chemoradiation or postoperative chemotherapy, which are much more difficult to tolerate. I favor a preoperative approach as outlined in this study.
Ultimately, the researchers should be congratulated for such a good attempt to improve outcomes among a group of patients who are in high need of clinical investigation. Currently, chemoradiation remains a very reasonable standard of care for these patients.

Reference:
Shapiro J, et al. Lancet Oncol. 2015;doi:10.1016/S1470-2045(15)00040-6.

Theodore S. Hong, MD

Massachusetts General Hospital Cancer Center

Disclosures: Hong reports no relevant financial disclosures.