ZD1839 Provides Some Clinical Benefit in Advanced Breast Cancer

March 1, 2003

CHICAGO-The novel biologic agent ZD1839 (gefitinib; Iressa) provided some clinical benefit, and may have relieved bone pain, in heavily pretreated patients with advanced breast cancer, according to results of a recent phase II trial. Of 63 patients treated, 9 or 14.3% had a partial response or stable disease, and 15% of patients remained on treatment for 4 to 8 months or longer

CHICAGO—The novel biologic agent ZD1839 (gefitinib; Iressa) provided some clinical benefit, and may have relieved bone pain, in heavily pretreated patients with advanced breast cancer, according to results of a recent phase II trial. Of 63 patients treated, 9 or 14.3% had a partial response or stable disease, and 15% of patients remained on treatment for 4 to 8 months or longer

Some patients remained on therapy, even as disease progressed, because they had marked relief of bone pain, said investigator Kathy S. Albain, MD, professor of medicine at Loyola University Medical Center in Chicago. "A not insignificant subset of patients may have achieved benefit…and additional patients had major relief of bone pain, despite objective progression," said Dr. Albain.

Early Clinical Data

The findings presented by Dr. Albain represent some of the first clinical data for ZD1839 in breast cancer. ZD1839 is an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), a key modulator of tumor cell function. ZD1839 has already attracted considerable attention in the scientific community and popular media for investigations in solid tumors, most notably non-small-cell lung cancer.

In this multicenter study, 1839IL/0156, women with metastatic breast cancer (median age 52 years) received ZD1839 at 500 mg/day until disease progression or withdrawal due to toxicity. Twenty-seven women (43%) were hormone receptor-positive and 50 (79%) had visceral disease.

Most of the women (49 patients, or 78%) had at least two prior chemotherapy regimens for metastatic disease, while 34 (54%) had one or more prior hormonal therapies. About one-third had received trastuzumab (Herceptin). In addition, most patients also had prior adjuvant chemotherapy with or without hormonal therapy.

Generally Well Tolerated

Dr. Albain said that ZD1839 was generally well tolerated at the 500 mg dose, and short treatment interruptions helped ameliorate toxicity. For four patients, the dose was reduced to 250 mg because of toxicity, as allowed by study protocol.

Grade 3 or 4 toxicity occurred in 16 patients (25%), mostly grade 3 nausea, vomiting and diarrhea. An acneiform rash occurred in 28 patients (44%), including four cases that were grade 3 or 4. "The toxicity profile was very similar to that observed in single-agent trials in advanced lung cancer," Dr. Albain said.

Of the nine patients that had a response or stable disease, three met stringent criteria for clinical benefit (disease response or stabilization for at least 6 months), including one partial responder with widespread metastases, and two with stable disease. An additional six patients had stable disease for up to 6 months.

Median progression-free survival was 57 days, and median survival was 144 days at the time of this analysis. Fifteen percent stayed on treatment for 4 to 8 months or longer, and 39 patients were still alive as of the time of the analysis.

Bone Pain Relief

Bone pain was reported by 12 patients at study enrollment. Although the trial was not designed to assess bone pain, investigators observed that five of these patients (42%) had marked bone pain relief. "Several stopped all scheduled narcotics," Dr. Albain said. "In fact, two remained on ZD1839, despite objective progression, because of major palliation of pain."

Taken together, "these findings support additional study of this novel agent in breast cancer, but in different settings," such as in combination with chemotherapy, or perhaps even specifically in breast cancer patients with bone pain, Dr. Albain said.

Meanwhile, molecular studies are in progress, looking at EGFR expression and other biomarker assessments in tumor cells. These will be reported later this year. Investigators hope that the results will give them a better idea of which metastatic breast cancers would most likely benefit from this therapy.

"Results of the molecular correlative analyses underway will be used to inform the design of future studies," said Dr. Albain.