Lani
10-02-2006, 02:01 PM
Lapatinib Shows Promise in Inflammatory Breast Cancer
Allison Gandey
October 2, 2006 (Istanbul) –- GlaxoSmithKline's experimental new drug lapatinib (Tycerb) may offer patients with recurrent inflammatory breast cancer an important alternative. "For these patients with limited options, it is very well tolerated," study author Bella Kaufman, MD, from the Chaim Sheba Medical Center in Tel Hashomer, Israel, told reporters here at the 31st Congress of the European Society of Medical Oncology (ESMO).
"We saw remarkable responses in these women," lead investigator Maureen Trudeau, MD, from the Sunnybrook Health Center in Toronto, Ontario, told Medscape during an interview. "These patients tried multiple therapies and they had relapsed and relapsed and relapsed, so for this to act on the tumor with minimal toxicity is very encouraging." Dr. Trudeau said she would like to see lapatinib started earlier in this patient population.
During a breast cancer discussion evaluating the findings, session cochair Martine Piccart, MD, from the Jules Bordet Institute in Brussels, Belgium, called the study "very small and hypothesis-generating." But she acknowledged that the drug does appear to be highly active in the setting of inflammatory breast cancer.
"I think she's right in that it's a small subset of patients," Dr. Trudeau told Medscape. "But that's always going to be the problem in inflammatory breast cancer because it's only 1% to 2% of the population. You're never going to have a large enough group in a short enough time to do a randomized study unless you did it quite widely. I think this demonstrates an unmet need in this group of patients, who may have rapidly progressive disease in spite of the availability of something like Herceptin."
Limited Treatment Options for Inflammatory Breast Cancer
Genentech's trastuzumab, sold under the brand name Herceptin, is an ErbB2 inhibitor and has been used in inflammatory breast cancer. Lapatinib is an orally bioavailable reversible ErbB1 and ErbB2 inhibitor. In the present analysis, the investigators evaluated the overall response rate to lapatinib in patients with inflammatory breast cancer with recurrent disease or who were refractory to prior anthracycline therapy.
The researchers looked at 47 patients divided into 2 cohorts (32 patients in the first group and 15 in the second). In Cohort A, which included ErbB2-positive subjects, they found that 44% experienced a partial response to lapatinib and 6% had a complete response. In Cohort B, which included ErbB1-positive and ErbB2-negative patients, they found that 6.7% experienced a partial response to therapy. The researchers reported that 70% of patients had evidence of dermal-lymphatic invasion at time of initial diagnosis.
The investigators conclude that lapatinib is generally well tolerated, with only grade 1 and 2 gastrointestinal and skin-related adverse events. There were 5 deaths in the cohort that the researchers say were most likely due to disease progression.
"Lapatinib monotherapy is clinically active in heavily pretreated inflammatory breast cancer patients," Dr. Trudeau said during her presentation. "There was a 50% response rate in tumors overexpressing ErbB2 and a 7% response rate in tumors expressing ErbB1."
Inflammatory breast cancer affects younger patients, most under the age of 50 years at diagnosis, and has the worst survival rate. Considered the most aggressive form of breast cancer, 35% of patients have metastatic disease at time of diagnosis. "Inflammatory breast cancer patients need to be in trials," Dr. Trudeau emphasized to Medscape. "This is a population that we need to thoroughly investigate."
No Apparent Cardiotoxicity
In another presentation at the same session, Edith Perez, MD, from the Mayo Clinic in Jacksonville, Florida, presented cardiac data for lapatinib. "There has always been a concern that anything that is ErbB targeted might be associated with congestive heart failure or large drops in ejection fractions," Dr. Trudeau said, noting that trastuzumab has been linked with heart problems.
But in a surprise finding, the researchers observed that in 3500 carefully monitored patients, only 0.2% experienced cardiac events. "This is really almost no incidence," Dr. Perez said. "I would have expected that in the general population, so we're very impressed by the cardiac safety of lapatinib."
Dr. Trudeau said her team had a similar experience with the cardiac safety of the drug. "In terms of the patients we've seen on study, this result is not surprising because they haven't had any problems either." But Dr. Piccart cautioned that this new cardiac safety study might be subject to selection bias. During a discussion following the session, she said that many of the patients randomized to lapatinib, an ErbB inhibitor, likely had strong hearts to begin with due to the potential safety concern.
"I think lapatinib is definitely going to be useful," Dr. Trudeau told Medscape. "I think in time it will be used more widely after Herceptin. It will provide a new therapy, but as for the comparison and whether it will prove to be better than Herceptin or how the 2 should be divided as first-line therapies remains to be determined."
ESMO 31st Congress: Abstracts 140O and 142O. Presented October 1, 2006.
Allison Gandey
October 2, 2006 (Istanbul) –- GlaxoSmithKline's experimental new drug lapatinib (Tycerb) may offer patients with recurrent inflammatory breast cancer an important alternative. "For these patients with limited options, it is very well tolerated," study author Bella Kaufman, MD, from the Chaim Sheba Medical Center in Tel Hashomer, Israel, told reporters here at the 31st Congress of the European Society of Medical Oncology (ESMO).
"We saw remarkable responses in these women," lead investigator Maureen Trudeau, MD, from the Sunnybrook Health Center in Toronto, Ontario, told Medscape during an interview. "These patients tried multiple therapies and they had relapsed and relapsed and relapsed, so for this to act on the tumor with minimal toxicity is very encouraging." Dr. Trudeau said she would like to see lapatinib started earlier in this patient population.
During a breast cancer discussion evaluating the findings, session cochair Martine Piccart, MD, from the Jules Bordet Institute in Brussels, Belgium, called the study "very small and hypothesis-generating." But she acknowledged that the drug does appear to be highly active in the setting of inflammatory breast cancer.
"I think she's right in that it's a small subset of patients," Dr. Trudeau told Medscape. "But that's always going to be the problem in inflammatory breast cancer because it's only 1% to 2% of the population. You're never going to have a large enough group in a short enough time to do a randomized study unless you did it quite widely. I think this demonstrates an unmet need in this group of patients, who may have rapidly progressive disease in spite of the availability of something like Herceptin."
Limited Treatment Options for Inflammatory Breast Cancer
Genentech's trastuzumab, sold under the brand name Herceptin, is an ErbB2 inhibitor and has been used in inflammatory breast cancer. Lapatinib is an orally bioavailable reversible ErbB1 and ErbB2 inhibitor. In the present analysis, the investigators evaluated the overall response rate to lapatinib in patients with inflammatory breast cancer with recurrent disease or who were refractory to prior anthracycline therapy.
The researchers looked at 47 patients divided into 2 cohorts (32 patients in the first group and 15 in the second). In Cohort A, which included ErbB2-positive subjects, they found that 44% experienced a partial response to lapatinib and 6% had a complete response. In Cohort B, which included ErbB1-positive and ErbB2-negative patients, they found that 6.7% experienced a partial response to therapy. The researchers reported that 70% of patients had evidence of dermal-lymphatic invasion at time of initial diagnosis.
The investigators conclude that lapatinib is generally well tolerated, with only grade 1 and 2 gastrointestinal and skin-related adverse events. There were 5 deaths in the cohort that the researchers say were most likely due to disease progression.
"Lapatinib monotherapy is clinically active in heavily pretreated inflammatory breast cancer patients," Dr. Trudeau said during her presentation. "There was a 50% response rate in tumors overexpressing ErbB2 and a 7% response rate in tumors expressing ErbB1."
Inflammatory breast cancer affects younger patients, most under the age of 50 years at diagnosis, and has the worst survival rate. Considered the most aggressive form of breast cancer, 35% of patients have metastatic disease at time of diagnosis. "Inflammatory breast cancer patients need to be in trials," Dr. Trudeau emphasized to Medscape. "This is a population that we need to thoroughly investigate."
No Apparent Cardiotoxicity
In another presentation at the same session, Edith Perez, MD, from the Mayo Clinic in Jacksonville, Florida, presented cardiac data for lapatinib. "There has always been a concern that anything that is ErbB targeted might be associated with congestive heart failure or large drops in ejection fractions," Dr. Trudeau said, noting that trastuzumab has been linked with heart problems.
But in a surprise finding, the researchers observed that in 3500 carefully monitored patients, only 0.2% experienced cardiac events. "This is really almost no incidence," Dr. Perez said. "I would have expected that in the general population, so we're very impressed by the cardiac safety of lapatinib."
Dr. Trudeau said her team had a similar experience with the cardiac safety of the drug. "In terms of the patients we've seen on study, this result is not surprising because they haven't had any problems either." But Dr. Piccart cautioned that this new cardiac safety study might be subject to selection bias. During a discussion following the session, she said that many of the patients randomized to lapatinib, an ErbB inhibitor, likely had strong hearts to begin with due to the potential safety concern.
"I think lapatinib is definitely going to be useful," Dr. Trudeau told Medscape. "I think in time it will be used more widely after Herceptin. It will provide a new therapy, but as for the comparison and whether it will prove to be better than Herceptin or how the 2 should be divided as first-line therapies remains to be determined."
ESMO 31st Congress: Abstracts 140O and 142O. Presented October 1, 2006.