1. Samson, Kurt

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SAN FRANCISCO-Using PET to monitor esophageal cancer patients' response to chemotherapy, and switching agents when one is ineffective, improved patient response more than four-fold, according to data from a phase II study presented at the ASCO 2017 Gastrointestinal Cancers Symposium (Abstract 1).

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Findings from the federally funded clinical trial could point to a new way to gauge tumor response to initial chemotherapy, thereby enabling doctors to tailor further chemotherapy, according to Karyn Goodman, MD, Medical Director of Clinical Trials at the University of Colorado Cancer Center in Aurora.


The study, by the Alliance for Clinical Trials in Oncology, is among the first to demonstrate the potential benefits of using PET to help inform and guide pre-surgical treatment decisions, Goodman told a press briefing.


"Adding induction chemotherapy before chemoradiation and using PET scans to assess response can help doctors make quick course corrections to maximize patient benefit from chemotherapy," she noted.


"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, meaning there were no traces of cancer in the tissue specimen taken at the time of surgery."


Study Specifics

The trial involved 257 patients with stage T3/4 or N1 disease who were randomized into two different chemotherapy regimens, carboplatin/paclitaxel or FOLFOX6, after a baseline PET scan to assess disease status. Another scan was performed 36-42 days after chemotherapy.


Response was set at 35 percent or greater decrease in PET standardized uptake value (SUV), and those who responded to treatment continued with the same chemotherapy regimen. Those who did not were switched to the other regimen for chemoradiation.


The primary objective was to improve the pathologic complete response (pCR) in nonresponders from 5 percent, the historical rate, to 20 percent with the PET-guided strategy. Patients who switched to a different regimen on the basis of a negative PET scan had a pCR rate of 18 percent.


Of patients who could be evaluated, 57 percent of those in the FOLFOX6 induction group responded to initial treatment, while 30 percent did not. In the carboplatin/paclitaxel arm, 50 percent met PET response criteria and 38 percent did not.


Subsequent pCR rates among patients who continued randomized therapy during chemoradiation were 31 percent in the FOLFOX6 arm and 12.5 percent in the carboplatin/paclitaxel group. Among patients who did not respond to randomized therapy and were switched to the alternate regimen, pCR rates were 19 percent in the FOLFOX6 subjects and 17 percent in the carboplatin/paclitaxel group.


Combined, the pCR rate for all PET nonresponders was 18 percent. Both the study's primary endpoint and efficacy criteria were met in both of the groups.


Patients who met PET response criteria after induction therapy (both arms combined) had a pCR rate of 26 percent, and the pCR rate for the entire study population was 22.7 percent.



Briefing moderator Nancy Baxter, MD, PhD, of St. Michael's Hospital and the University of Toronto, said the study is a step forward toward more personalized and effective treatment.


"PET scans may prove to be a valuable tool to help oncologists fine-tune the use of chemotherapy for esophageal cancer and maximize the benefit of chemotherapy for each individual patient," said Baxter. "This is heartening evidence for a new approach to treating a disease where innovation is sorely needed."


A number of recent studies have shown the benefits of preoperative chemoradiation for patients with operable esophageal or gastroesophageal junction (GEJ) cancer, but even with effective treatment, 5-year survival is 50 percent or less. Most patients die of systemic disease, and ongoing research in the field focuses on identifying more effective systemic therapies to optimize treatment. Evaluation of those therapies would benefit from better ways to identify them, said Goodman.


Several previous studies that looked at patients who received preoperative chemoradiation showed that those patients who achieved pCR at the time of surgery had better overall and disease-free survival.


A recent review of multiple prospective studies demonstrated the feasibility of using PET to determine response to induction chemotherapy and to discontinue treatment early when patients do not respond, and confirmed that a negative posttreatment PET scan identified patients with a poor prognosis.


"This really helps move the field forward in terms of finding personalized ways of better treating our patients, particularly those who are responding poorly to the therapy we initially offered them and to people who have been diagnosed with these very hard to treat cancers," said Baxter. Early response assessment using PET can be incorporated into future studies to identify more effective new regimens for esophageal and cancers, she added.


"We know pCR is a prognostic marker and we will be getting the additional information in terms of patient survival in this study in the next 6 months or so," Goodman noted.


It is important to understand whether systemic treatment with chemotherapy is effective, but that is difficult when chemotherapy is given together with radiation therapy, said Daniela Molena, MD, Director of esophageal surgery at Memorial Sloan Kettering Cancer Center in New York.


"This trial is very important and we have adopted this approach for our patients at MSK," she told Oncology Times. "Testing if the chemotherapy is actually working by measuring the effect on the tumor activity with PET SUV gives us the opportunity to change treatment in patients who are not responders, hopefully increasing their chances."


From the study's results, she continued, FOLFOX might be a better systemic therapy with higher pathological complete response in both responders and non-responders when compared to carbo/taxol.


"Even in patients who started with carbo/taxol and crossed over to FOLFOX, the pathological complete response is optimistic. Pathological complete response, however, does not necessarily mean 'cure,' so it will be very important to wait for longer results."


Kurt Samson is a contributing writer.