The combination of trastuzumab (Herceptin) and lapatinib (Tykerb) resulted in an overall objective response rate of 30% in heavily pretreated patients with HER2-positive metastatic colorectal cancer, according to findings presented at the annual meeting of the American Association for Cancer Research.

Of 33 patients, 2 patients achieved complete responses and 8 had partial responses, while 13 patients achieved stable disease. This brought the total clinical benefit rate to 70% at the time of data cutoff on Feb. 28.

“There is a large unmet need in colorectal cancer,” said study author, Silvia Marsoni, MD , director of the precision medicine unit at the Istituto di Candiolo, Fondazione del Piemonte per l’Oncologia–IRCCS in Turin, Italy.

“The combination of drugs really had a great impact on the tumor,” said Dr. Marsoni, who discussed the findings at a presscast. “One of these complete responders is still alive without evidence of disease at almost 36 months from the beginning of his treatment. This was a very good duration of response.”

HER2 amplification is found in 5% of RAS wild-type metastatic colorectal cancer cases. Dual HER2 blockade with both trastuzumab and lapatinib had inhibited tumor growth in preliminary studies, but that has not been the case for either drug used alone.

The HERACLES trial was conducted at four centers in Italy and enrolled 33 patients with RAS wild-type, HER2-positive tumors that were refractory to standard of care treatments, including the epidermal growth factor receptor (EGFR) inhibitors cetuximab and panitumumab.

“These patients were heavily pretreated and 75% had four or more prior treatments,” explained Dr. Marsoni.

All participants received trastuzumab intravenously with a 4 mg/kg loading dose followed by 2 mg/kg weekly, and lapatinib was given orally at 1,000 mg daily. Treatment continued until disease progression.

The primary endpoint was the objective response rate, and secondary endpoints included progression-free survival and safety.

The two patients who achieved a complete response continue to be disease free, and both had tumors that were refractory to cetuximab and resistant to all standard treatment.

Historically, the response rate in metastatic colorectal cancer after second-line treatment is very low, at less than 5% with chemotherapy and about 10%-20% with anti-EGFR therapy.

“There was really no toxicity,” explained Dr. Marsoni. “We used a lapatinib dose that was about 20% less than what is used in breast cancer to avoid GI toxicity.”

Only six patients (18%) experienced grade 3 side effects, which included fatigue, skin rash, and elevated bilirubin.

“In conclusion, we can say that, even if HER2-positive patients in colon cancer are only 3% of the population, they are still a little and important piece of the cake that can be actively targeted with a new chemotherapy-free regimen,” said Dr. Marsoni. “We have a new potential treatment for this population.”