In what is described as a new paradigm to individualize treatment of esophageal and gastroesophageal junction (GEJ) cancers, researchers have shown that positron emission tomography (PET) can help guide chemotherapy decisions for patients and improve outcomes.
As clinicians know, any improvement in outcomes in this setting is highly welcome, as 5-year survival rates are only 40% to 50%, said lead author, Karyn A. Goodman, MD, a radiation oncologist at the University of Colorado School of Medicine in Aurora.
She was discussing initial results from the phase 2 CALGB 80803 study at a presscast ahead of the 2017 Gastrointestinal Cancers Symposium in San Francisco, California.
Preoperative chemoradiotherapy is an accepted standard of care for patients with operable esophageal or GEJ adenocarcinoma (and has been shown to be superior to surgery alone), but the optimal chemotherapy is undefined, Dr Goodman explained: Several chemotherapy options could be used.
So her team decided to assess chemotherapy responsiveness with PET early on — right after induction therapy, so that another chemotherapy can still be tried during concurrent radiotherapy (and before surgery).
The study was conducted in 257 patients with stage II to III esophageal and GEJ adenocarcinoma, all of whom underwent PET and then were randomly assigned to one of two induction chemotherapy regimens: modified FOLFOX-6 (oxaliplatin, leucovorin, 5-fluoroucil) or carboplatin/paclitaxel.
PET was repeated after the first few cycles of induction therapy. If there was tumor shrinkage as assessed by PET (suggesting that the induction chemotherapy worked), then patients continued with the same chemotherapy regimen.
However, if the PET scan revealed that the induction chemotherapy regimen was not working, chemotherapy was changed to the other regimen. Overall, 39 of 129 patients who received FOLFOX-6 induction chemotherapy and 49 of 128 patients who received carboplatin/paclitaxel switched chemotherapy regimens after PET.
Overall, this strategy enabled 18.0% of the patients who were initial nonresponders (14 of 78; as assessed by PET) to move on to another chemotherapy regimen and ultimately achieve a pathologic complete response (pCR) upon completion of chemoradiotherapy.
The primary endpoint of the study was pCR (as indicated by PET) among the patients who crossed over to alternative chemotherapy.
Overall, the pCR rate was 26.0% among all PET responders (31 of 120) and 22.7% (45 of 198) among all patients who were evaluable in the study.
Dr Goodman pointed out that in prior studies, where presurgery chemotherapy was not changed based on a PET scan, the pCR rate among patients with tumors not responsive to induction chemotherapy was only 5%.
In other words, the new results are a substantial improvement over historical outcomes.
Importantly, pCR correlates with overall survival in this patient setting, Dr Goodman told reporters. "We know this is a prognostic marker," she said. More data from this trial, including results for progression-free survival, are expected in the next half-year, she added.
Dr Goodman acknowledged that the new approach of using a PET assessment lengthens a patient's time before surgery but emphasized that the results show that the information obtained from the PET scan improves the efficacy of treatment, as shown by the higher pCR rate that was achieved.
PET is covered by Medicare for staging and evaluation of treatment response for esophageal and GEJ cancers, she noted.
Moves the Field Forward
"This really helps move the field forward," said Nancy Baxter, MD, PhD, a surgeon from St Michael's Hospital in Toronto, Ontario, Canada, during the presscast, which she moderated. Dr Baxter, who is also an American Society of Clinical Oncology (ASCO) expert, pointed out that using PET scans for early assessment of response is "personalized" therapy.
"PET scans may prove to be a valuable tool to help oncologists fine-tune the use of chemotherapy for esophageal cancer," she said in ASCO meeting press materials.
Dr Goodman struck a more convinced note about the usefulness of this strategy. The new study "shows the benefit of a new paradigm" to individualize multimodality therapy, she said. Further early response assessment using PET can be incorporated into future studies to identify more effective regimens for esophageal and GEJ cancers, she added.
PET scans are regularly used to guide therapy in lymphoma but are only beginning to be explored for this purpose in solid tumors, according to ASCO.
This study was supported by grants from the National Institutes of Health. Dr Goodman reports a consulting or advisory role for Pfizer, and several coauthors also reported ties to industry. Dr Baxter has disclosed no relevant financial relationships.
2017 Gastrointestinal Cancers Symposium. Abstract 1. To be presented January 19, 2017.