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PET response after induction chemotherapy may predict esophageal cancer outcomes
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CHICAGO — PET scan response after induction chemotherapy may be a useful prognostic and predictive tool for esophageal cancer, according to findings presented at ASCO Annual Meeting.
“We are trying to better tailor therapy for patients with esophageal cancer because we don’t do as well as we would like and survival rates remain poor, even though the standard of care is a fairly aggressive regimen of chemotherapy and radiation followed by surgery,” Karyn A. Goodman, MD, Grohne chair of clinical oncology at University of Colorado, Denver, told HemOnc Today.
Goodman and colleagues evaluated the use of PET response after induction chemotherapy to direct changing to alternative chemotherapy during preoperative chemoradiation among 240 patients with resectable esophageal and gastroesophageal junction adenocarcinomas.
Results of the primary analysis showed improvement of pathologic complete response after changing the regimen among PET nonresponders.
The current analysis reported survival outcomes based on PET response status and the type of induction chemotherapy used.
“There is a need for early assessment for response to chemotherapy,” Goodman said. “We make use of PET for staging of esophageal cancer, so this use — as a prognostic tool based on PET response — is a novel approach.”
Eligible participants underwent baseline PET and then were randomly assigned to induction chemotherapy with modified FOLFOX-6 (oxaliplatin, leucovorin, 5-FU) on days 1, 15 and 29, or carboplatin/paclitaxel on days 1, 8, 22 and 29. Patients underwent a repeat PET scan on days 36 to 42.
PET nonresponders crossed over to the alternative chemotherapy regimen during chemoradiotherapy, with radiation given in 50.4 Gy over 28 fractions, whereas PET responders received the same chemotherapy during chemoradiation. Patients underwent surgery 6 weeks following chemoradiotherapy.
Over a median follow-up of 42.1 months, the researchers observed a median OS of 38.3 months.
Rates of OS were 61.7% at 2 years and 45.8% at 4 years.
PET responders achieved a median OS of 47.3 months compared with nonresponders at 28.9 months.
“By changing the chemotherapy regimen early on after induction chemotherapy, we saw better, longer-term survival by changing chemotherapy for patients who were initially PET nonresponders,” Goodman said. “The survival in the PET nonresponders was even better than we’ve seen in previous studies that have not changed chemotherapy in this poor-risk group.”
Other findings showed a median survival of more than 50 months for PET responders receiving induction and concurrent FOLFOX, according to Goodman.
“This represents one of the best outcomes for any patient group with esophageal cancer,” she said. “This finding possibly indicates that FOLFOX might be a better option in this population. However, our data set was not powered to evaluate a head-to-head comparison of the two induction regimens.”
Goodman concluded that the findings suggest that PET may be used as both a prognostic and predictive tool in patients with esophageal and gastroesophageal junction adenocarcinomas and can help individualize therapy for these patients with the goal of improving outcomes in this disease. – by Rob Volansky
Reference:
Goodman KA, et al. Abstract 4012. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Goodman reports consultant/advisory roles with Pfizer and RenovoRX. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Davendra Sohal, MD
The results of CALGB 80803 show that PET responders to preoperative chemotherapy have an improved OS — median 40 months vs. 27 months in nonresponders, which is in line with what we would expect — and PET response could be a surrogate marker of eventual outcome. Nonetheless, the role of PET in this setting remains investigational until longer-term outcomes of switching chemotherapy for initial nonresponders are available.
More interestingly, however, the FOLFOX arm demonstrated better OS than the carboplatin/paclitaxel arm (responders, 49 months vs. 31 months for responders; nonresponders, 31 months vs. 26 months). This leads to the question of what the chemotherapy backbone should be for preoperative chemoradiation in this setting. We need to learn more from this and other studies, putting in context the data from perioperative FLOT and postoperative FOLFOX studies, as well. Long-term outcomes will help answer the question better.
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Veena Shankaran, MD
This study addresses the utility of early PET scan in predicting response to neoadjuvant treatment and survival in locally advanced gastroesophageal junction/esophageal adenocarcinoma, a patient population that we commonly see and treat in the United States. A key finding of this study is that PET response to induction chemotherapy — with either regimen — clearly predicts improved survival. In other words, a good response to initial chemotherapy, regardless of the regimen chosen, results in a better outcome.
Another important finding of this study is that patients who exhibit lack of PET response to the initial chemotherapy regimen and, thus, are switched to the alternate chemotherapy drugs with concurrent radiation, have quite encouraging median survival — better than historical estimates — suggesting that a switch in chemotherapy might be beneficial. However, because the nonresponders were not randomly assigned to continuation vs. switch in chemotherapy regimen, we do not know the extent to which the switch in chemotherapy contributed to this survival outcome.
Finally, future studies should explore the safety and efficacy of FOLFOX induction plus FOLFOX chemoradiation given encouraging results with this regimen.
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