Trastuzumab fails to impress in lung cancer trial
Trastuzumab (Herceptin) has failed to improve outcomes for patients with non-small-cell lung cancer, a study reveals.
The patients were taking part in a trial to test whether trastuzumab
added any benefit to treatment with gemcitabine and cisplatin — standard
chemotherapy for non-small-cell lung cancer (NSCLC). However, those treated
with trastuzumab in combination with gemcitabine and cisplatin did no
better than patients treated with gemcitabine and cisplatin alone.
Trastuzumab is a humanised monoclonal antibody developed by Roche to
target cells that overexpress human epidermal growth factor receptor
2 (HER2). It provides clinical benefits in HER2-positive breast cancer
and has previously been shown to have antitumour activity in preclinical
models of lung cancer.
In the latest study, researchers led by Ulrich Gatzemeier, lung and chest
sugery centre, Grosshansdorf Hospital, Germany, randomly assigned 101
patients with HER2-positive NSCLC to receive either conventional chemotherapy
for up to six 21-day cycles or conventional chemotherapy plus trastuzumab.
They found no significant difference between response rates (41 per cent
for patients treated with conventional chemotherapy versus 36 per cent
for patients treated with trastuzumab). Progression-free survival was
also similar for the two groups. However, a small subgroup of patients
with strong overexpression of HER2 (HER2 3+) did seem to benefit from
addition of trastuzumab to their chemotherapy.
“
Five out of the six patients with extremely high levels of HER2 responded
better than other HER2 patients. It was nearly eight-and-a-half months
before their disease progressed,” said Dr Gatzemeier.
However, he added that the group of patients with the highest expression
of HER2 made up less than 2 per cent of the patients originally screened
for trial eligibility. “Our data suggest that although nearly 60
per cent of NSCLC patients overall are HER2 positive, any possible benefit
of trastuzumab is likely to be confined to under 5 per cent of all patients
with advanced NSCLC.” (Annals of Oncology 2004;15:19.)
Carsten Reinhardt, Roche’s international medical manager for Herceptin,
told The Journal that at the time the trial was designed, the HER2 expression
pattern of NSCLC was not so well known. “We now know that Herceptin
works best in HER2 3+ patients.” Dr Reinhardt added that the company
was concentrating on more promising disease areas, such as breast cancer. |
The
Pharmaceutical Journal