Expert Point of View: Nancy Baxter, MD, PhD & Steven H. Lin, MD, PhD


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Nancy Baxter, MD, PhD

Nancy Baxter, MD, PhD

“CALGB 80803 really helps move the field forward,” said press briefing moderator and ASCO spokesperson Nancy Baxter, MD, PhD, a surgeon from St. Michael’s Hospital in Toronto, Ontario, Canada. “PET [positron-emission tomography] scans may prove to be a valuable tool to help oncologists fine-tune the use of chemotherapy for esophageal cancer,” she commented.


Although the finding of high response rates with this regimen [FOLFOX6] is interesting, it’s not something to base our clinical decisions on yet.
— Steven H. Lin, MD, PhD

However, Steven H. Lin, MD, PhD, Associate Professor of Radiation Oncology at The University of Texas MD Anderson Cancer Center, Houston, was more cautious. “We can’t use this study as a basis for changing clinical management,” he told The ASCO Post.

Dr. Lin, who moderated the session where the results were presented, called the study “one of the most anticipated” of the symposium. “We’ve been waiting for these data since the study completed accrual this past year,” he said.

“The researchers achieved feasibility of a multicenter study using PET imaging as a response marker for esophageal adenocarcinomas, and this has never been done in esophageal cancer,” he said. “It’s a confirmative randomized trial based on a previous MUNICON trial showing that responders to induction chemotherapy had better outcomes and pathologic responses, and nonresponders had low [pathologic complete response] rates.1 They validated those findings, and that’s commendable. They also achieved the primary endpoint, which is to see whether switching chemotherapy in nonresponders achieves a higher [pathologic complete response] over what is expected for nonresponders, and it did.”

‘Biggest Surprise’

For Dr. Lin, the “biggest surprise” was that patients receiving carboplatin/paclitaxel as induction (before chemoradiation) had a pathologic complete response rate that was “substantially lower” than rates achieved in other studies of this regimen, especially the CROSS trial.2 In CROSS, he noted, pathologic complete responses were achieved by 23% of patients with adenocarcinomas who received carboplatin/paclitaxel plus radiotherapy (without induction chemotherapy).

“I think even the investigators were surprised by the relative inefficacy of carboplatin/paclitaxel, especially in light of other studies, both the CROSS and the NEOSCOPE trials, which used carboplatin/paclitaxel with radiotherapy,” continued Dr. Lin. “Most medical oncologists feel this is a good regimen, relatively nontoxic, and convenient. Its efficacy was good in the CROSS trial, and it is now widely held to be the standard chemotherapy regimen to be used with chemoradiation. To see the low [pathologic complete response] rate in a select group of PET responders was surprising.”

The CROSS trial also found median overall survival to be 49.4 months in the chemoradiotherapy/surgery group vs 24.0 months in the surgery-alone group (hazard ratio = 0.657; P = .003). The results of the CROSS trial made carboplatin/paclitaxel the standard-of-care chemotherapy regimen in many centers, he said.

In the current study, patients who received induction carboplatin/paclitaxel and achieved a response on PET had a pathologic complete response rate of only 12.5%. In PET nonresponders, who then switched to FOLFOX [leucovorin, fluorouracil, oxaliplatin], the rate was 17%.

“Even in a select population of responders, the [pathology complete response] after carboplatin/paclitaxel was only 12.5%, and this is surprising, because in the nonselected CROSS population, it was 23%, which is what we expect for adenocarcinomas,” Dr. Lin indicated.

In addition, among responders to initial modified FOLFOX6, the rate was 37.5%, “and that’s high and unexpected,” Dr. Lin further noted. For the subset not responding and therefore switching to carboplatin/paclitaxel, it was 19%.

Clinical Implications

“It’s interesting that FOLFOX6 produced a higher response rate. The study did not compare the regimens head to head, so we can’t draw conclusions from this, but the response rate with carboplatin/paclitaxel was lower,” said Dr. Lin. He noted that FOLFOX6 as the chemotherapy component of treatment has not been well studied in clinical trials, and although the finding of high response rates with this regimen is interesting, he said, “it’s not something to base our clinical decisions on yet. It’s hypothesis-generating for future trials.”

Dr. Lin also pointed out that the use of induction chemotherapy, itself, is not the standard of care. It may improve response rates, but its association with improved clinical outcomes has not been established yet in prospective randomized trials, he said.

“Can you improve survival based on a response assessment using PET? The jury is still out,” Dr. Lin concluded. “We need a phase III trial that incorporates induction chemotherapy for response assessment, then switching chemotherapy for nonresponse. Does that package improve survival outcomes, vs upfront chemoradiation without induction chemotherapy, which is still considered the standard of care at this point?” ■

Disclosure: Dr. Baxter reported no potential conflicts of interest. Dr. Lin has received research grants from STCube Pharmaceuticals, Roche/Genentech, Hitachi Chemical, Inc., Peregrine Pharmaceuticals, and Elekta Inc and honoraria from AstraZeneca, ProCure, US Oncology, and Elekta Inc.

References

1. Lordick F, Ott K, Krause BJ, et al: PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: The MUNICON phase II trial. Lancet Oncol 8:797-805, 2007.

2. van Hagen P, Hulshof MC, van Lanschot JJ, et al: Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366:2074-2084, 2012.


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