Julia Draznin Maltzman, MD
Abramson Cancer Center of the University of Pennsylvania
Today, on this anniversary of D-Day, ASCO was bursting with new information and data. Details of presentations can be found on OncoLink for CME credit, but below is a brief summary of major themes discussed.
There were a number of presentations on hematologic malignancies presented today. For the most part investigators examined the definition of remission in leukemia and multiple myeloma. Thought provoking information was presented in regards to hematologic, cytogenetic, and molecular responses to therapies, however little consensus was reached. Best front line therapies for multiple myeloma and acute promeylocytic leukemia are still unclear as there are many new and effective agents. Perhaps the most interesting data presented regards the use of targeted therapies. Specific agents that received much attention in various diseases included: thalidomide, Bortezomib, IMMU-10 (conjugated doxorubicin to CD 47), Arsenic, Lipo-ATRA, Imatinib, Rituximab, Alemtuzumab, and BL22 (conjugated pseudomoal toxin to CD 22). This further substantiates the claim that we are moving in the direction of targeted therapies to all malignancies.
A large validation study of the online prognostic model called Adjuvant! was presented. The model allows physicians to put some basic prognostic data for the patient and a risk benefit assessment of further therapy is provided. This study sought to validate this model as clinically useful. It was noted that there was a very tight correlation of the prediction of this model and the actual outcome. This model will undoubtedly will go on to be used by many oncologists while evaluating the benefit of further therapy.
The new antinausea medication called Aprepitent was demonstrated as an important agent with cisplatin based chemotherapy. One trial presented looked at the effectiveness of this drug in adriamycin and cyclophosphomide based therapy - the most common treatment for breast cancer. The drug had a statistically significant improvement in the nausea and vomiting experienced by breast cancer patients. The conclusion of the study is that this agent is safe and effective in this disease and should be offered to patients.
In the metastatic setting, an EORTC phase III trial showed that exemustane had a higher progression free survival over Tamoxifen in postmenopausal women. This trial would imply that exemustane has the same efficacy and magnitude as the non-steroidal aromatase inhibitors used in breast cancer.
The new tyrosine kinase dual inhibitor of both Her1 and Her 2 showed some efficacy in heavily pretreated metastatic breast cancer patients. The agent known as Lapatinib or GW 572016 showed an overall response rate of 10% in this population of patients.
Abraxane, or ABI-007, showed some activity in taxane refractory metastatic breast cancer patients with good tolerability. The effect was modest, however, the patients were heavily pretreated and even a modest response is considered a positive finding.
Bortezomib, the proteosome inhibitor was found to have no activity in breast caner, with zero percent response in a small trial. Other new targeted agents did show some promise such as Temsirolumus, vinflunine (also called Javlor, an anti-tubulin agent), and Ixabepilone a new epothilone.
This year we saw confirmation of last year's ASCO plenary session, of adjuvant cisplatin based therapy for early stage operable lung cancer. A number of trials presented supported this finding and confirmed this treatment as the new standard of care. This is a paradigm shift in the treatment of lung cancer as it imparts a survival advantage to a disease which is notoriously unresponsive to treatment. Taken as an aggregate, the presented data would suggest that new clinical trials should focus on neoadjuvant versus adjuvant therapy.
In the setting of locally advanced unrespectable disease a CALGB trial examined the possibility of induction chemotherapy. There was no survival advantage seen with the institution of induction chemotherapy for this disease. The next question is to examine the use of maintenance therapy.
Combination trials of chemotherapy with targeted small molecules again did not show a survival advantage in the metastatic lung cancer trials examined. We will be eagerly waiting for the recently accrued ECOG trial of combination Avastin and chemotherapy for lung cancer.
Single agent Erlotinib or OSI-774, was found to be superior to supportive care. Erbitux was noted to have single agent activity with a 6% response rate in advanced disease. And, consistent with the recent papers in the New England Journal of Medicine and Nature, it was again noted that only those individuals with the recognized mutation in the EGFR gene respond to Iressa. A handful of responders did not harbor the mutation. This finding may imply that they have other mutations that are targets for the tyrosine kinase inhibitors.
The long awaited trial in adjuvant colorectal cancer showed Xeloda to have an improved disease free survival over 5-FU and have fewer side effects. Another trial examining the combination of irinotecan with 5FU versus 5FU alone showed a similar overall survival and disease free survival but much more toxicity and even death. A European study compared three months of continuous infusion 5FU to six months of bolus therapy. The shorter treatment was found to be less toxic with a similar overall survival. It would be important to note the MOSAIC study reported in this week's New England Journal of Medicine that showed a survival advantage to adjuvant FOLOFX therapy. All the above stated trials are for adjuvant disease for stage III patients. The QUASAR trial was finally reported examining adjuvant therapy for stage II disease. The risk of recurrence was decreased with 5FU therapy and a modest 3% increase in survival was noted. However, critics site, the 8% of stage III disease patients included in the study, the 29% rectal cancer patients, and the unknown lymph node status.
In the field of rectal cancer one trial examined the use of pre-operative radiation therapy with and without chemotherapy. It was noted that combination neoadjuvant therapy is superior to radiation alone. The study also showed that responses obtained pre-operatively predicted survival for these patients.
An interesting study examined whether or not a three-year disease free survival can serve as an endpoint to a cancer therapy trial. The study noted that 73% of all recurrences occur in the first three years and that there is a very tight correlation between three and five year survival. This study is noteworthy as many of our treatment decisions are based on three-year survival data. These results will likely have tremendous impact on our data interpretation and policy changes.
One of the more important GI trials to be presented today is the confirmatory Erbitux trial where a 12% response rate was noted. The initial trial showed a similar (10%) response rate but a large-scale confirmatory trial needed to be completed.
Avastin did not show promise in heavily pre-treated individuals who progressed on irinotecan.
A CALGB trial concluded that sentinel lymph node collection did not correlate with survival in colon cancer as it does in breast cancer. The number of involved lymph nodes is important for prognosis as well as their size but a full dissection may be necessary.
The biggest news came in renal cell cancer came in the news that a novel tubulin stabilizer called BMS247550 had a response rate in this difficult to treat disease. This was truly surprising as no other taxane has shown any activity renal cell.
Metaloproteases again showed no activity in prostate cancer and radical prostatectomy, external beam radiation therapy, and brachytherapy all had equivalent responses in prostate cancer.