In a late-breaking abstract presented at the 1st European Lung Cancer Conference jointly organized by the International Association for the Study of Lung Cancer (IASLC) and the European Society for Medical Oncology (ESMO), Prof. Giorgio Scagliotti from the University of Torino, Italy presented data from the clinical trial stopped in February.
For some patients, the drug results in worse outcomes. "Based on a planned interim analysis the study showed a clear inferiority from adding sorafenib to carboplatin/paclitaxel in first-line non-small-cell lung cancer patients with squamous histology," Prof. Scagliotti said.
Sorafenib is an oral multikinase inhibitor with anti-angiogenic and antiproliferative activity. The drug, marketed as Nexavar by Bayer, is already approved for use in more than 40 countries for liver cancer and more than 70 countries for renal cell cancer.
The latest trial included 926 patients with unresectable stage IIIB/IV non-small-cell lung cancer who had received no prior systemic treatment. Patients were randomized to receive carboplatin plus paclitaxel, combined with either sorafenib 400 mg or placebo.
After a formal review of the ongoing study, the trial's data monitoring committee recommended termination. Preliminary results showed a median overall survival of 10.7 months in the sorafenib group vs 10.6 months in the placebo arm. Sorafenib-treated patients with squamous-cell non-small-cell lung cancer had a greater mortality rate than those with non-squamous histology.
"To date there is no evidence of any detrimental effect from sorafenib in additional subgroups of patients," Prof. Scagliotti said.
He noted that researchers are still studying the drug in lung cancer, including an ongoing study examining adding it to the combination of cisplatin and gemcitabine.-European Society for Medical Oncology
Nexavar Dropped From Lung Cancer Trial
It's a shame about the Nexavar clinical trial. It reminds me of the Iressa debacle. It actually did work miracles in some patients. Cell function analysis has found that a cellular signal for response to the drug can identify some responders, but this limits Iressa's market profile significantly.
To the manufacturer, what good is the drug if it cannot be used by a broad base of the population? How will drug companies respond when studies show their drug to be highly effective, but only in 10-15% of the potential patient population? A failure? No, not by a long shot!
Combination chemotherapy has not always produced greater degrees of clinical benefit than single agent therapy, as this clinical trial illustrates. When two or more drugs are given, there is a greater probability that at least one of the drugs will be active. There is then the potential for true synergery, where the whole is greater than the sum of the parts.
But most drug combinations are only additive or at most, minimally synergistc. However, some newer combinations show greater degrees of synergy, although apparently not in this study. True synergy is rather uncommon in most adult solid tumors. Most drug combinations in diseases are merely additive, where the whole equals the sum of its parts, and not synergistic. In hematologic neoplasms (leukemia, lymphoma, multiple myeloma), true synergy is very common.
In cases like this study, where drugs are only additive and not synergistic, nothing is learned by testing the drugs in combination compared to what is learned by testing them separately. Therefore, drugs in combination are only tested in cases where there is the realistic possiblitiy of seeing true synergy.
The best combinations are those in which there is true synergy and in which the toxicities of the drugs in the combination are non-overlapping, so that full doses of each drug may be given safely.
The era of empiric, aggressive, multi-agent cytotoxic chemotherapy for first-line/recurrent/refractory adult solid tumors should come to an end. More emphasis should be put on matching treatment to patient, through the use of individualized genetic and cellular pre-testing.