- Email: [email protected]
Tyrosine kinase inhibitors: who will benefit?
Newsdesk
Neoadjuvant combination for stage II–III breast cancer French researchers suggest that neoadjuvant chemotherapy with trastuzumab, docetaxel, and carboplatin can be an effective treatment option for stage II or III ERBB2-positive breast cancer (J Clin Oncol, published online May 21, 2007; DOI:10.1200/ JCO.2006.09.9994). ERBB2 overexpression in breast cancer results in aggressive disease, early peak of local relapse or metastasis after primary surgery, and poor prognosis. Trastuzumab—a drug that selectively binds with ERBB2 receptor—provides clinical benefits in ERBB2-positive breast cancer. The drug activates immunological functions, inhibits the ERBB2 extracellular domain, and decreases ERBB2 phosphorylation. Bruno Coudert (Centre Georges François Leclerc, Dijon, France) and co-workers enrolled 70 patients with stage II or III, ERBB2-positive
operable breast cancer. 67 of the patients received, before surgery, six 3-week cycles with trastuzumab, docetaxel, and carboplatin. The other three patients could not receive the six cycles of treatment, as one patient developed progressive disease after two cycles and two patients had to be withdrawn from treatment because of toxicity. After treatment, 59 patients had a clinical complete response and seven had a partial response, with favourable tolerability. Using Chevallier criteria (a criteria for evaluating pathological responses to chemotherapy), the researchers noted that 20 patients had no evidence of tumour at the primary site or the lymph nodes, and an additional seven patients showed evidence of only carcinoma in situ. In an intent-to-treat analysis, tumour and nodal pathological complete response (a prognostic indicator for
prolonged disease-free and overall survival) was noted in 27 of the patients. “The results of this study confirm the high rate of pathological complete response of a docetaxel [and] trastuzumab combination with an addition of carboplatinum”, says coauthor Joseph Gligorov (Hôpital Tenon, Paris, France). “The most important drug is trastuzumab, but synergy with taxanes and particularly docetaxel clearly explains that the best pathological complete responses are obtained with this combination.” Aman Buzdar (MD Anderson Cancer Center, Houston, TX, USA) comments, “this study does illustrate that this combination causes significant benefit and may be an option for patients who are not candidates for anthracyclinecontaining combinations”.
Sanjit Bagchi
Tyrosine kinase inhibitors: who will benefit?
http://oncology.thelancet.com Vol 8 July 2007
examining tumour tissue, which is not always available. The researchers used mass spectrometry to examine pretreatment blood samples collected during three trials of EGFR TKIs, and developed an algorithm that related eight features of the spectra to the patients’ outcomes. They then tested the algorithm on two independent patient cohorts. In one validation cohort, the median survival in the predicted good outcome and poor outcome groups was 207 days and 92 days, respectively (HR 0·5; 95% CI 0·24–0·78); in the other, it was 306 days versus 107 days (0·41; 0·17–0·63). “These results appear robust and promising”, comments Jeffrey Engelman (Massachusetts General Hospital, Boston, MA, USA). But because the researchers did not assess tumours for other markers of response to EGFR TKIs (eg, EGFR and K-Ras mutations), whether or not mass spectrometry
data improves on these markers is unclear. Nevertheless, he adds, “a serum-based test that might predict benefit from the use of EGFR TKIs is particularly appealing”.
Jane Bradbury
Geoff Tompkinson/Science Photo Library
Mass spectrometry could be used to identify which patients with nonsmall-cell lung cancer (NSCLC) will benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as erlotinib, reports David Carbone (Vanderbilt-Ingram Cancer Center, Nashville, TN, USA) and colleagues (JNCI 2007; 99: 838–46). Their massspectrometry-based algorithm classifies patients with NSCLC into good or poor outcome groups after treatment with these drugs. “I was really surprised when the protein pattern we identified in three training sets of patients worked when we applied it blind to additional cohorts of patients”, says Carbone. But, he warns, the algorithm needs testing in prospective randomised trials. Current techniques for deciding which patients with NSCLC will benefit from EGFR TKIs—only about 40% of them seem to do so—depend on
Mass spectrometry can identify patients for treatment
579
Neoadjuvant combination for stage II–III breast cancer French researchers suggest that neoadjuvant chemotherapy with trastuzumab, docetaxel, and carboplatin can be an effective treatment option for stage II or III ERBB2-positive breast cancer (J Clin Oncol, published online May 21, 2007; DOI:10.1200/ JCO.2006.09.9994). ERBB2 overexpression in breast cancer results in aggressive disease, early peak of local relapse or metastasis after primary surgery, and poor prognosis. Trastuzumab—a drug that selectively binds with ERBB2 receptor—provides clinical benefits in ERBB2-positive breast cancer. The drug activates immunological functions, inhibits the ERBB2 extracellular domain, and decreases ERBB2 phosphorylation. Bruno Coudert (Centre Georges François Leclerc, Dijon, France) and co-workers enrolled 70 patients with stage II or III, ERBB2-positive
operable breast cancer. 67 of the patients received, before surgery, six 3-week cycles with trastuzumab, docetaxel, and carboplatin. The other three patients could not receive the six cycles of treatment, as one patient developed progressive disease after two cycles and two patients had to be withdrawn from treatment because of toxicity. After treatment, 59 patients had a clinical complete response and seven had a partial response, with favourable tolerability. Using Chevallier criteria (a criteria for evaluating pathological responses to chemotherapy), the researchers noted that 20 patients had no evidence of tumour at the primary site or the lymph nodes, and an additional seven patients showed evidence of only carcinoma in situ. In an intent-to-treat analysis, tumour and nodal pathological complete response (a prognostic indicator for
prolonged disease-free and overall survival) was noted in 27 of the patients. “The results of this study confirm the high rate of pathological complete response of a docetaxel [and] trastuzumab combination with an addition of carboplatinum”, says coauthor Joseph Gligorov (Hôpital Tenon, Paris, France). “The most important drug is trastuzumab, but synergy with taxanes and particularly docetaxel clearly explains that the best pathological complete responses are obtained with this combination.” Aman Buzdar (MD Anderson Cancer Center, Houston, TX, USA) comments, “this study does illustrate that this combination causes significant benefit and may be an option for patients who are not candidates for anthracyclinecontaining combinations”.
Sanjit Bagchi
Tyrosine kinase inhibitors: who will benefit?
http://oncology.thelancet.com Vol 8 July 2007
examining tumour tissue, which is not always available. The researchers used mass spectrometry to examine pretreatment blood samples collected during three trials of EGFR TKIs, and developed an algorithm that related eight features of the spectra to the patients’ outcomes. They then tested the algorithm on two independent patient cohorts. In one validation cohort, the median survival in the predicted good outcome and poor outcome groups was 207 days and 92 days, respectively (HR 0·5; 95% CI 0·24–0·78); in the other, it was 306 days versus 107 days (0·41; 0·17–0·63). “These results appear robust and promising”, comments Jeffrey Engelman (Massachusetts General Hospital, Boston, MA, USA). But because the researchers did not assess tumours for other markers of response to EGFR TKIs (eg, EGFR and K-Ras mutations), whether or not mass spectrometry
data improves on these markers is unclear. Nevertheless, he adds, “a serum-based test that might predict benefit from the use of EGFR TKIs is particularly appealing”.
Jane Bradbury
Geoff Tompkinson/Science Photo Library
Mass spectrometry could be used to identify which patients with nonsmall-cell lung cancer (NSCLC) will benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as erlotinib, reports David Carbone (Vanderbilt-Ingram Cancer Center, Nashville, TN, USA) and colleagues (JNCI 2007; 99: 838–46). Their massspectrometry-based algorithm classifies patients with NSCLC into good or poor outcome groups after treatment with these drugs. “I was really surprised when the protein pattern we identified in three training sets of patients worked when we applied it blind to additional cohorts of patients”, says Carbone. But, he warns, the algorithm needs testing in prospective randomised trials. Current techniques for deciding which patients with NSCLC will benefit from EGFR TKIs—only about 40% of them seem to do so—depend on
Mass spectrometry can identify patients for treatment
579