SAN FRANCISCO — There is now more evidence that adding targeted agents to standard treatment offers no benefit to patients with esophageal cancer.
In a randomized phase 3 trial, there was no significant difference in overall survival — the primary end point — or the complete response rate at 2 years when cetuximab (Erbitux) was added to concurrent chemoradiation.
In addition, when the RTOG 0436 investigators looked histology, there was no significant difference between patients with adenocarcinoma and those with squamous cell carcinoma; the survival curves overlapped at 2 years.
Once again, an epidermal growth-factor receptor (EGFR) inhibitor failed to improve survival in unselected patients treated nonoperatively with chemoradiation, said lead author Mohan Suntharalingam, MD, professor of radiation oncology at the University of Maryland School of Medicine in Baltimore.
He presented the study results here at the 2014 Gastrointestinal Cancers Symposium.
Dr. Suntharalingam and colleagues hypothesized that adding cetuximab to chemoradiation would improve 2-year survival from 41% to 53% (hazard ratio, 0.71). They also planned an interim analysis of complete clinical response (cCR).
"A survival advantage has been shown with concurrent chemotherapy and radiation," said Dr. Suntharalingam. "We have collectively worked hard to improve outcome with patients diagnosed with this disease."
The design of this study was modeled on a phase 2 study that demonstrated a benefit with EGFR inhibitors combined with chemotherapy and radiation, and on phase 3 studies of other disease sites, he explained.
Study discussant Manish Shah, MD, from Weill Cornell Medical College in New York City, pointed out that this study was well designed and performed but, "unfortunately, there was no survival difference."
"Cetuximab does not improve survival or response when combined with chemoradiation. This is consistent with previous results in metastatic disease," said Dr. Shah.
The results show that the clinical response to chemotherapy and radiation is prognostic, he noted. "The best approach for improving survival in this disease is to improve response to therapy."
No Survival Difference
All 328 patients with squamous cell carcinoma (n = 125) or adenocarcinoma (n = 203) of the esophagus (T1N1M0; T2 to 4 any N M0; any T/N M1a) were enrolled in the study from 2008 to 2013. They received weekly concurrent cisplatin 50 mg/m² and paclitaxel 25 mg/m², plus daily radiation (50.4 Gy delivered in1.8 Gy fractions). Patients randomized to the cetuximab group also received a loading dose of cetuximab 400 mg/m² on day 1 and then weekly cetuximab 250 mg/m².
The cohort was stratified by histology, tumor size (<5 cm="" nbsp="" vs="">5 cm), and the absence or presence of celiac lymph nodal involvement. Overall, 80% of the patients had T3/4 disease, 66% had N1 disease, and 19% had celiac nodal involvement.
Median follow-up was 15.4 months. Overall survival was similar for the cetuximab and control groups at 12 months (64% vs 65%; P = .70) and at 24 months (44% vs 42%; P = .70).
Table. Similar Survival for Squamous Cell Carcinoma and Adenocarcinoma
| Overall Survival | Cetuximab Group, % | Control Group, % |
| Squamous cell carcinoma | ||
| 12 months | 62 | 67 |
| 24 months | 46 | 43 |
| Adenocarcinoma | ||
| 12 months | 65 | 64 |
| 24 months | 43 | 41 |
Clinical Response Predictive of Survival
The cCR rate was similar in the cetuximab and control groups (56% vs 59%; P = .72), and there was no difference in cCR between patients with squamous cell carcinoma and those with adenocarcinoma.
For patients with cCR, the 12-month overall survival rate was 79% and the 24-month rate was 58%; for those with residual disease, the 12-month rate was 53% and the 24-month rate was 30% (P < .0001).
Dr. Suntharalingam noted that adverse events were evenly distributed in both treatment groups but, "not surprisingly," dermatologic events were higher in the cetuximab group.
On multivariate analysis, the 2 predictors of overall survival were Zubrod/ECOG performance status and tumor lesion size, which is consistent with previous literature.
"We had the opportunity to look at patients' endoscopic response 6 to 8 weeks after the completion of therapy," Dr. Suntharalingam explained. "What we found was that patients who achieved a clinical response at 6 to 8 weeks had an improved overall survival. This held for both adenocarcinoma and squamous cell carcinoma. So we found that endoscopic response at 6 to 8 weeks was predictive of overall survival."
The study was supported by RTOG CA21661 and CCOP CA3742 NCI grants and by Bristol-Myers Squibb. The authors have disclosed no relevant financial relationships.
2014 Gastrointestinal Cancers Symposium (GICS): Abstract LBA6. Presented January 16, 2014.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου