Dual HER2 therapy added to CRT for esophageal cancer is tolerable, active

Adding dual HER2-targeted therapy to neoadjuvant chemoradiotherapy is a well tolerated and efficacious treatment strategy in patients with resectable esophageal adenocarcinoma positive for this receptor, a multicenter phase 2 TRAP trial suggests.

Survival of esophageal cancer with neoadjuvant chemoradiotherapy alone remains poor, note senior investigator Hanneke W. M. van Laarhoven, MD, PhD, Amsterdam University Medical Center, University of Amsterdam, Cancer Center Amsterdam, and coinvestigators. But 15%-43% of tumors are positive for HER2, raising the possibility that targeted therapy could improve outcomes for some.

The investigators enrolled in the TRAP trial 40 patients with resectable HER2-positive adenocarcinoma of the esophagus or gastroesophageal junction. Among the patients, 78% were men, and the median age was 63 years. Planned treatment for all patients consisted of neoadjuvant chemoradiotherapy with carboplatin and paclitaxel in weeks 1 through 5, plus both trastuzumab (Herceptin) and pertuzumab (Perjeta) in weeks 2 through 13, then surgery in week 14.

Trial results reported in the Journal of Clinical Oncology showed that 83% of the patients completed treatment with trastuzumab and pertuzumab, meeting the predefined 80% threshold for feasibility of this treatment.

There were no unexpected safety events. Some 48% of patients had grade 3 or worse adverse events (mainly diarrhea and dysphagia), and 28% had serious adverse events (mainly vomiting, nausea, and gastrointestinal hemorrhage).

Of the 38 patients who underwent surgery, all achieved a complete (R0) resection and 34% achieved a pathologic complete response.

With a median follow-up of 32.1 months, the 3-year rates of progression-free survival and overall survival were 72% and 71%, respectively.

Compared with a cohort of similar patients from the Netherlands Cancer Registry who received conventional neoadjuvant chemoradiotherapy and were matched on propensity score (but not HER2 status), the trial patients had a significantly lower risk of death (hazard ratio, 0.58; 95% confidence interval, 0.34-0.97).

 

Neither pharmacokinetic measures nor tumor activity on [¹⁸F]fluorodeoxyglucose positron emission tomography predicted outcomes. But patients whose tumors had 3+ immunohistochemical HER2 expression had better overall survival (P = .007), and patients whose tumors were positive for growth factor receptor-bound protein 7 (Grb7) had a better treatment response (P = .016).

“This is the first study to our knowledge demonstrating the feasibility of the addition of both trastuzumab and pertuzumab to standard neoadjuvant chemoradiotherapy with carboplatin and paclitaxel in patients with resectable HER2-positive esophageal adenocarcinoma ... ” Dr. van Laarhoven and coinvestigators wrote.

“[T]he addition of trastuzumab and pertuzumab to neoadjuvant chemoradiotherapy is safe and tolerable for patients with HER2-positive esophageal adenocarcinoma, and preliminary efficacy results seem promising,” they concluded. “Because data on an HER2-positive control group are lacking, a randomized phase III study is warranted to demonstrate the superiority of the addition of trastuzumab and pertuzumab.”

Dr. van Laarhoven disclosed honoraria from Lilly/ImClone; a consulting or advisory role with Lilly/ImClone, Nordic Group, Bristol-Myers Squibb, and Servier; research funding to her institution from numerous pharmaceutical companies; and travel, accommodations, and/or expenses from AstraZeneca. The study was supported by the Academic Medical Center, Amsterdam, and by an unrestricted research grant from Hoffmann-LaRoche, Basel, Switzerland.

SOURCE: Stroes CI et al. J Clin Oncol. 2019 Dec 6. doi: 10.1200/JCO.19.01814.

Adding dual HER2-targeted therapy to neoadjuvant chemoradiotherapy is a well tolerated and efficacious treatment strategy in patients with resectable esophageal adenocarcinoma positive for this receptor, a multicenter phase 2 TRAP trial suggests.

Survival of esophageal cancer with neoadjuvant chemoradiotherapy alone remains poor, note senior investigator Hanneke W. M. van Laarhoven, MD, PhD, Amsterdam University Medical Center, University of Amsterdam, Cancer Center Amsterdam, and coinvestigators. But 15%-43% of tumors are positive for HER2, raising the possibility that targeted therapy could improve outcomes for some.

The investigators enrolled in the TRAP trial 40 patients with resectable HER2-positive adenocarcinoma of the esophagus or gastroesophageal junction. Among the patients, 78% were men, and the median age was 63 years. Planned treatment for all patients consisted of neoadjuvant chemoradiotherapy with carboplatin and paclitaxel in weeks 1 through 5, plus both trastuzumab (Herceptin) and pertuzumab (Perjeta) in weeks 2 through 13, then surgery in week 14.

Trial results reported in the Journal of Clinical Oncology showed that 83% of the patients completed treatment with trastuzumab and pertuzumab, meeting the predefined 80% threshold for feasibility of this treatment.

There were no unexpected safety events. Some 48% of patients had grade 3 or worse adverse events (mainly diarrhea and dysphagia), and 28% had serious adverse events (mainly vomiting, nausea, and gastrointestinal hemorrhage).

Of the 38 patients who underwent surgery, all achieved a complete (R0) resection and 34% achieved a pathologic complete response.

With a median follow-up of 32.1 months, the 3-year rates of progression-free survival and overall survival were 72% and 71%, respectively.

Compared with a cohort of similar patients from the Netherlands Cancer Registry who received conventional neoadjuvant chemoradiotherapy and were matched on propensity score (but not HER2 status), the trial patients had a significantly lower risk of death (hazard ratio, 0.58; 95% confidence interval, 0.34-0.97).

 

Neither pharmacokinetic measures nor tumor activity on [¹⁸F]fluorodeoxyglucose positron emission tomography predicted outcomes. But patients whose tumors had 3+ immunohistochemical HER2 expression had better overall survival (P = .007), and patients whose tumors were positive for growth factor receptor-bound protein 7 (Grb7) had a better treatment response (P = .016).

“This is the first study to our knowledge demonstrating the feasibility of the addition of both trastuzumab and pertuzumab to standard neoadjuvant chemoradiotherapy with carboplatin and paclitaxel in patients with resectable HER2-positive esophageal adenocarcinoma ... ” Dr. van Laarhoven and coinvestigators wrote.

“[T]he addition of trastuzumab and pertuzumab to neoadjuvant chemoradiotherapy is safe and tolerable for patients with HER2-positive esophageal adenocarcinoma, and preliminary efficacy results seem promising,” they concluded. “Because data on an HER2-positive control group are lacking, a randomized phase III study is warranted to demonstrate the superiority of the addition of trastuzumab and pertuzumab.”

Dr. van Laarhoven disclosed honoraria from Lilly/ImClone; a consulting or advisory role with Lilly/ImClone, Nordic Group, Bristol-Myers Squibb, and Servier; research funding to her institution from numerous pharmaceutical companies; and travel, accommodations, and/or expenses from AstraZeneca. The study was supported by the Academic Medical Center, Amsterdam, and by an unrestricted research grant from Hoffmann-LaRoche, Basel, Switzerland.

SOURCE: Stroes CI et al. J Clin Oncol. 2019 Dec 6. doi: 10.1200/JCO.19.01814.

Adding dual HER2-targeted therapy to neoadjuvant chemoradiotherapy is a well tolerated and efficacious treatment strategy in patients with resectable esophageal adenocarcinoma positive for this receptor, a multicenter phase 2 TRAP trial suggests.

Survival of esophageal cancer with neoadjuvant chemoradiotherapy alone remains poor, note senior investigator Hanneke W. M. van Laarhoven, MD, PhD, Amsterdam University Medical Center, University of Amsterdam, Cancer Center Amsterdam, and coinvestigators. But 15%-43% of tumors are positive for HER2, raising the possibility that targeted therapy could improve outcomes for some.

The investigators enrolled in the TRAP trial 40 patients with resectable HER2-positive adenocarcinoma of the esophagus or gastroesophageal junction. Among the patients, 78% were men, and the median age was 63 years. Planned treatment for all patients consisted of neoadjuvant chemoradiotherapy with carboplatin and paclitaxel in weeks 1 through 5, plus both trastuzumab (Herceptin) and pertuzumab (Perjeta) in weeks 2 through 13, then surgery in week 14.

Trial results reported in the Journal of Clinical Oncology showed that 83% of the patients completed treatment with trastuzumab and pertuzumab, meeting the predefined 80% threshold for feasibility of this treatment.

There were no unexpected safety events. Some 48% of patients had grade 3 or worse adverse events (mainly diarrhea and dysphagia), and 28% had serious adverse events (mainly vomiting, nausea, and gastrointestinal hemorrhage).

Of the 38 patients who underwent surgery, all achieved a complete (R0) resection and 34% achieved a pathologic complete response.

With a median follow-up of 32.1 months, the 3-year rates of progression-free survival and overall survival were 72% and 71%, respectively.

Compared with a cohort of similar patients from the Netherlands Cancer Registry who received conventional neoadjuvant chemoradiotherapy and were matched on propensity score (but not HER2 status), the trial patients had a significantly lower risk of death (hazard ratio, 0.58; 95% confidence interval, 0.34-0.97).

 

Neither pharmacokinetic measures nor tumor activity on [¹⁸F]fluorodeoxyglucose positron emission tomography predicted outcomes. But patients whose tumors had 3+ immunohistochemical HER2 expression had better overall survival (P = .007), and patients whose tumors were positive for growth factor receptor-bound protein 7 (Grb7) had a better treatment response (P = .016).

“This is the first study to our knowledge demonstrating the feasibility of the addition of both trastuzumab and pertuzumab to standard neoadjuvant chemoradiotherapy with carboplatin and paclitaxel in patients with resectable HER2-positive esophageal adenocarcinoma ... ” Dr. van Laarhoven and coinvestigators wrote.

“[T]he addition of trastuzumab and pertuzumab to neoadjuvant chemoradiotherapy is safe and tolerable for patients with HER2-positive esophageal adenocarcinoma, and preliminary efficacy results seem promising,” they concluded. “Because data on an HER2-positive control group are lacking, a randomized phase III study is warranted to demonstrate the superiority of the addition of trastuzumab and pertuzumab.”

Dr. van Laarhoven disclosed honoraria from Lilly/ImClone; a consulting or advisory role with Lilly/ImClone, Nordic Group, Bristol-Myers Squibb, and Servier; research funding to her institution from numerous pharmaceutical companies; and travel, accommodations, and/or expenses from AstraZeneca. The study was supported by the Academic Medical Center, Amsterdam, and by an unrestricted research grant from Hoffmann-LaRoche, Basel, Switzerland.

SOURCE: Stroes CI et al. J Clin Oncol. 2019 Dec 6. doi: 10.1200/JCO.19.01814.