In patients with resectable esophageal or gastroesophageal junction cancer, positron-emission tomography (PET) imaging was used to assess response to induction chemotherapy. PET nonresponders were identified after the first few cycles and were switched to an alternate regimen. This strategy greatly improved the patients’ chances of achieving a pathologic complete response, researchers reported at the 2017 Gastrointestinal Cancers Symposium.¹

PET scans are routinely used to guide treatment in lymphoma but are only beginning to be explored for this purpose in solid tumors. This study is among the first to show the benefit of PET imaging in esophageal cancer, specifically for dictating treatment before surgery.

— Karyn A. Goodman, MD

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Karyn A. Goodman, MD, a radiation oncologist at the University of Colorado School of Medicine in Aurora, led the randomized phase II Cancer and Leukemia Group B (CALGB) 80803 study that found PET assessment and switching chemotherapy increased the rate of pathologic complete response to 18%, compared with a historical rate of 5%. (CALGB is now the Alliance for Clinical Trials in Oncology.)

“In this study, we are adding induction chemotherapy before chemoradiotherapy and showing that using PET scans after several cycles of chemotherapy to assess response can help doctors make quick course corrections to maximize patient benefit from chemotherapy,” Dr. Goodman said.

She suggested the use of metabolic imaging is “a new paradigm” for this cancer, one that may help “individualize multimodality therapy and improve outcomes in this poor-prognosis population.” PET scans are routinely used to guide treatment in lymphoma but are only beginning to be explored for this purpose in solid tumors. This study is among the first to show the benefit of PET imaging in esophageal cancer, specifically for dictating treatment before surgery, she said.

CALGB 80803

The study was conducted in 257 patients with stage T3/4 or N1 esophageal and gastroesophageal junction adenocarcinoma. All patients underwent baseline PET scans and then were randomly assigned to one of two induction chemotherapy regimens: modified FOLFOX6 (fluorouracil, leucovorin, oxaliplatin) or carboplatin/paclitaxel. After several cycles—36 to 42 days of treatment—­patients had a repeat PET scan.

If standardized uptake values decreased by ≥ 35% from baseline, the patient was considered a responder and continued on the same chemotherapy regimen during the chemoradiotherapy component of treatment. If this was not achieved, the patient was deemed a nonresponder and was switched to the alternative regimen during chemoradiotherapy. Surgery was performed approximately 6 weeks after the completion of chemoradiotherapy.

The primary objective was to improve the pathologic complete response rate in nonresponders to induction therapy from the 5% historical rate seen in patients who continued on the same chemotherapy during chemoradiation to 20% by changing chemotherapy during chemoradiation. The primary endpoint of the study was pathologic complete response at the time of surgery among the patients who crossed over to alternative chemotherapy. The study met this endpoint in both treatment cohorts.

Outcomes

Overall, 39 of 129 patients who received FOLFOX6 induction chemotherapy and 49 of 128 patients who received carboplatin/paclitaxel switched chemotherapy regimens after PET. For patients starting on the FOLFOX6 regimen, 57% of evaluable patients were PET responders. In the carboplatin/paclitaxel arm, 50% were PET responders. After completion of chemoradiotherapy and surgical resection, the pathologic complete response rate was 26.0% among all PET responders and 18.0% among patients initially not responding to induction and therefore switching treatment.

Although the study was not powered to compare the two induction regimens, patients who responded to FOLFOX6 appeared to be more likely to achieve a pathologic complete response after chemoradiotherapy: 37.5% vs 12.5% for the carboplatin/paclitaxel group. “FOLFOX induction and concurrent therapy resulted in a very promising pathologic complete response rate,” Dr. Goodman commented.

“Although our approach does lengthen a patient’s time before surgery, we found that assessing treatment efficacy by PET scans can improve the efficacy of the treatment, as shown by the ability to achieve a pathologic complete response,” she said.

Pathologic complete response has been correlated with overall survival in this setting, she added, noting, “We know this is a prognostic marker.” Progression-free survival will be analyzed later this year. ■

Disclosure: This study was supported by grants from the National Institutes of Health. Dr. Goodman reports a consulting or advisory role for Pfizer.

Reference

1. Goodman KA, Niedzwiecki D, Hall N, et al: Initial results of CALGB 80803 (Alliance). 2017 Gastrointestinal Cancers Symposium. Abstract 1. Presented January 19, 2017.