A 2008 Research Note to a Friend on Renal Cancer

What I did back then, was to discuss several treatment options for renal cell carcinoma so the friend of my friend could form an opinion on what was best for him. Ideally, he then discussed these options with 2-4 oncologists including his lead doctor and got their point of view, thus reaching the best decision based on all the opinions.

“First, on the treatment currently being considered, he needs to understand that it is a mid-stage trial designed to test the safety and efficacy of AMG-386. At this stage in development, AMG-386 has not been conclusively shown to be effective and its toxicity profile is being tested. The study has 3 groups and patients are randomly assigned to each. In one group patients receive AMG-386 alone; there is a possibility that patients in this group will not get any clinical benefit, but they could still get toxic effects from the drug. In another group, AMG-386 will be used in conjunction with Nexavar; again, there is a chance that patients here will not get any additional efficacy relative to Nexavar alone, but could still experience increased toxic effects. The third group is Nexavar alone, which some physicians use as the first treatment for about 20% of their patients with no poor prognostic factors. For the remaining 80%, they use Sutent [generic name – sunitinib].

At this point, your friend seems to be in good physical shape, or what doctors call performance status, given that one requisite for participating in the AMG-386 trial is that patients have adequate organ and hematological function. If that’s the case, he may want to consider starting his treatment with Sutent, which appears to be more effective than Nexavar as an initial [first-line] treatment, but is more toxic. Nevertheless, he may be able to tolerate it given his current performance status.

The evidence is the following: In similar first-line studies, Sutent produced a median progression-free survival [PFS], a measure of disease progression, of 11 months vs 5 months for interferon alpha, the previous standard of care before the introduction of Sutent and Nexavar to the market. This result was highly statistically significant [P<0.00001]. Nexavar has so far produced no PFS advantage vs. interferon [5.6 months vs. 5.7 months, respectively, based on the first 121 progression events]. Sutent’s toxicity included grade 3-4 [severe-very severe] neutropenia in 12% of patients, grade 3-4 fatigue in 7% of patients, and grade 3-4 diarrhea in 5% of patients. In comparison, a different trial of Nexavar with treatment experienced patients resulted in grade 3 hand-foot rash in 5% of patients, and other grade 3 events including hypertension, fatigue, and diarrhea in only 2% or less of patients.

Some oncologists feel more data is needed to know if Sutent benefits outweight the side effects, but still believe the data so far clearly suggest that Sutent is the more potent agent, so it’s their agent of choice as the initial [first-line] treatment. Nexvar, however, has been demonstrated to be a strong drug for 2nd line therapy [patients that failed prior systemic therapy]. Torisel [CCI-779] is another drug that has demonstrated significant activity in severely refractory patients. Given their different mechanisms of action, an alternative first-line regimen for your friend may be a combination of Sutent with Nexavar and/or Torisel. Such regimens have not been tested yet, but they will since they are likely to be more effective than Sutent alone, so they may be worth trying now if possible to manage their related toxicities. It may be best to implement strongly toxic regimens for relative short periods to avoid cumulative side effects.

Additional potential treatments are the following: RAD001 [generic name everolimus] from Novartis, a drug acting through the same mechanism as Torisel, with the added advantage of being more effective and oral, will likely become available by early 2009. A regimen of Avastin [a drug already available on the market] and interferon has so far shown activity in renal cancer and is also likely to be approved for that indication in early 2009. Also, the combination of Avastin and Tarceva [both available] is considered an active regimen that has produced highly encouraging data thus far. Finally, Pfizer is developing a follow-on product to Sutent called axitinib [generic name], and is in mid-stage trials.

Finally, I recently came across http://www.blochcancer.org/, a support website dedicated to “help all cancer patients in the process to successfully conquer their disease”, which appears to be worth visiting.

Please tell you friend that he can contact me at any time if he has questions or if there is anything else I can help with.”