By Mary Welch
Herceptin used in conjunction with chemotherapy slows the progression of cancer and increases tumor shrinkage in HER2-overexpressing tumors found in women with metastatic breast cancer, according to Phase III data presented by Genentech Inc. at the American Society of Clinical Oncology (ASCO) conference, in Los Angeles.
If Herceptin (trastuzumab), designated by the FDA as a fast track product, is approved, it will be the first potential treatment for HER2-overexpressing metastatic breast cancer, a particularly brutal and aggressive cancer.
Genentech, of South San Francisco, filed for marketing approval of Herceptin in May and released preliminary results of the Phase III trials in December. (See BioWorld Today, May 5, 1998, p. 2, and Dec. 23, 1997, p. 1.)
The company's stock (NYSE:GNE) closed Monday at $72.375, up $2.375.
Herceptin is a humanized anti-HER2 monoclonal antibody. Nearly one-third of all women with breast cancer have tumors that overexpress HER2, a growth factor receptor.
The Phase III trial, conducted with 469 women who had tumors that overexpressed HER2 but who had not been given chemotherapy, showed patients treated with the monoclonal antibody and chemotherapy experienced tumor progression later than patients undergoing chemotherapy alone.
Time To Disease Progression Slows 65 Percent
In the study, half the patients were given Herceptin with paclitaxel or with anthracycline plus cyclophosphamide. The other half received chemotherapy alone. The median time to disease progression was slowed by 65 percent (from 4.6 months to 7.6 months) for women receiving Herceptin and chemotherapy compared with those who just had chemotherapy.
Twenty-eight percent of patients who received Herceptin did not show any evidence of tumor growth at one year, compared with 14 percent of the women undergoing chemotherapy alone.
Of the women who received Herceptin and chemotherapy, 49 percent experienced a complete or partial response (tumor shrinkage of 50 percent or greater), compared with 32 percent of those receiving chemotherapy.
Clinical benefits were found in both chemotherapy combinations with Herceptin, but were greater with paclitaxel.
In a second trial, Herceptin alone was given to 222 women who had relapsed following one or more chemotherapy treatments. The overall response rate was 16 percent, with four patients showing a complete response and 26 a partial response. Median duration of response was nine months.
While those receiving Herceptin alone experienced chills and fevers, an increased risk of cardiac dysfunction was observed in women receiving Herceptin and chemotherapy, particularly anthracyclines.
"The side effects are potentially severe but they can be managed by medication," said Genentech spokeswoman Marie Kennedy. "They are not to be taken lightly and we are conducting future studies."
Genentech, along with Idec Pharmaceuticals Inc., of San Diego, Calif., also reported on a Phase II study with Rituxan, a monoclonal antibody approved by the FDA for relapsed or refactory low-grade follicular non-Hodgkin's lymphoma.
The trial tested Rituxan in patients with previously untreated intermediate or high-grade non-Hodgkin's lymphoma. The data showed a 97 percent response rate in 33 patients given Rituxan with standard chemotherapy.
Thirty-two out of 33 patients, when given Rituxan with CHOP (a standard chemotherapy regime of cyclophosphamide, doxorubicin, vincristine and prednisone), responded to treatment, with 24 complete responses, eight partial responses and one progression.
"This was a very small study," said Kennedy. "We have started larger multicenter Phase II trials to compare the safety and efficacy results of Rituxan and chemotherapy vs. chemotherapy alone.
Idec discovered Rituxan and developed the product in collaboration with Genentech; Hoffmann-LaRoche Ltd., of Basel, Switzerland; and Zenyaku Kogyo Co. Ltd. of Japan.
In other news presented at ASCO:
* Vical Inc., of San Diego, will expand Phase II and Phase III multi-center trials of Allovectin-7 in patients with metastatic melanoma. In the Phase II trial, enrollment will be open to patients with metastatic, refractory, Stage III or IV disease that has not spread to other organs. Up to 70 advanced melanoma patients will be enrolled. The objective is partial or complete response in at least 15 percent of the evaluable patients, persisting with a median duration of at least four months.
The Phase III trial will determine the efficacy of Allovectin-7 when combined with standard chemotherapy in patients with unresectable, metastatic melanoma not treated previously with chemotherapy. About 140 patients will be enrolled. Endpoints are either an improvement of at least two months in the median time to disease progression with no decrease in the rate of objective clinical responses or an improvement of at least 15 percent in the rate of objective clinical responses with no decrease in the median time to disease progression.
Allovectin's active ingredient is a gene encoding HLA-B7, an antigen responsible for triggering strong immune responses.
Vical also will start Phase II trials with Leuvectin in patients with metastatic renal cell carcinoma, the most common form of kidney cancer. The open-label, multi-center trial is designed to evaluate the safety and efficacy of Leuvectin in up to 80 patients with metastatic kidney cancer and determine response rate and duration. Leuvectin's active ingredient is a gene encoding interleukin-2, a naturally occurring protein that stimulates the immune system.
* Coulter Pharmaceutical Inc., of Palo Alto, Calif., reported encouraging preliminary results from a Phase II trial of Bexxar in 32 (out of a planned 60 ) patients with low-grade and transformed low-grade non-Hodgkin's lymphoma (NHL). The initial data showed all of the newly diagnosed patients with advanced low-grade NHL responded to Bexxar, with 71 percent experiencing complete disappearance of the disease. In addition, no evidence of NHL was detected at molecular levels using PCR analysis in nine patients. The trial is ongoing at the University of Michigan, in Ann Arbor. Bexxar is a radiolabeled monoclonal antibody. To date, complete remissions continue in 16 patients; however, eight of the 32 patients have relapsed. *