Michael Rotkowitz, MD, medical oncologist, Cancer Treatment Centers of America, Eastern Regional Medical Center, says that one of the main challenges and a leading goal of immunotherapy research is measuring response to justify the treatment and costs.

The scrutiny surrounding the immunotherapy sipuleucel-T (Provenge) stems from the fact that there is no tool to monitor response. Despite this scrutiny, other immunotherapies are also being researched for prostate cancer, including ipilimumab, GVAX, and PROSTAVAC.

Ipilimumab is being studied in a phase III trial compared to placebo in treatment-resistant metastatic prostate cancer patients.

GVAX was examined in a phase III trial comparing it to docetaxel plus prednisone for men with asymptomatic or minimally symptomatic castration-resistant prostate cancer (CRPC). The trial showed that the toxicity profile of GVAX was favorable to the combination arm but survival was not significantly improved.

The examination of PROSTVAC for asymptomatic or minimally symptomatic CRPC is underway in a phase III trial and uses pox viral vectors to stimulate the immune system.

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Michael Rotkowitz, MD, says that one of the main challenges and a leading goal of immunotherapy research is measuring response to justify the administration.

Dr. Rotkowitz Describes Challenges Facing Immunotherapy

Michael Rotkowitz, MD, medical oncologist, Cancer Treatment Centers of America, Eastern Regional Medical Center, discusses a phase III trial that was presented at the 2012 ESMO Congress that examined the immunotherapy ipilimumab (Yervoy) plus dacarbazine for patients with metastatic melanoma.

In the trial, 502 patients with unresectable metastatic melanoma received dacarbazine at 850 mg/m2 for 22 weeks and were further randomized 1:1 to receive either 10 mg/kg of ipilimumab or placebo on weeks 1, 4, 7, and 10. At a long-term follow-up, the trial demonstrated an improvement in overall survival (OS) of 19.0% for patients receiving ipilimumab compared to 9.6% in the control arm.

Rotkowitz explains that the 10 mg/kg dose of ipilimumab administered in this trial is controversial, since the approved dose for metastatic melanoma is 3 mg/kg. However, this trial has demonstrated benefits for using 10 mg/kg and has shown sustainable 3- and 4-year survival data for the first time in metastatic melanoma.

Michael Rotkowitz, MD, from Cancer Treatment Centers of America, discusses a phase III trial that examined ipilimumab plus dacarbazine for patients with metastatic melanoma. 

Dr. Rotkowitz on Ipilimumab Plus Dacarbazine for Melanoma

Michael Rotkowitz, MD, medical oncologist, Cancer Treatment Centers of America, Eastern Regional Medical Center, explains that the movement towards the use of targeted therapies and personalized medicine has resulted in the use of genetic markers and gene expression to help determine the best therapy.

However, Rotkowitz does not believe the personalization of medicine should stop at targeted therapy. He stresses that to truly personalize care each patient should be treated as an individual and not just a number in a trial. Not only should their genetics be considered but also their nutritional and physical well-being, which may require supplements, physical, or occupational therapy.

This type of mind-body approach allows the patient to get the most out of their therapy. Giving a targeted therapy to a patient who has a strong support system and a strong quality of life results in a better outcome.

Dr. Michael Rotkowitz, from Cancer Treatment Centers of America, Defines Personalized Medicine

Dr. Rotkowitz Defines Personalized Medicine

Michael Rotkowitz, MD, medical oncologist, Cancer Treatment Centers of America, Eastern Regional Medical Center, discusses the side effects associated with the combination of dabrafenib and trametinib, two investigational agents for advanced melanoma.

The current standard of care for advanced melanoma with a 

 mutation is the targeted agent vemurafenib. Rotkowitz explains that most patients taking this agent will experience some form of side effect. However, he remains optimistic that the investigational combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib will avoid many of these side effects.

Data from the phase I/II study investigating the combination suggests that the occurrence of side effects such as squamous cell carcinoma and other benign tumors was less common than in vemurafenib alone, while demonstrating a similar survival benefit.

Dr. Michael Rotkowitz, from Cancer Treatment Centers of America, on Dabrafenib and Trametinib Combination Side Effects

Dr. Rotkowitz on BRAF/MEK Combination Side Effects

Michael Rotkowitz, MD, medical oncologist, Cancer Treatment Centers of America, Eastern Regional Medical Center, discusses bypassing resistance in patients with melanoma that are receiving vemurafenib.

Rotkowitz notes that melanoma has been at the forefront of new pharmaceutical developers, in recent years. This includes the immunotherapy ipilimumab and the BRAF inhibitor vemurafenib. However, in some cases the responses to these medications will only last a few months before resistance is acquired. This makes studying the mechanisms of resistance very important.

In many cases, tumors bypass BRAF inhibition using the MEK pathway. This resistance pathway established the rational behind the combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib.

Rotkowitz notes that early data has shown that the combination helped control the tumor and even limited the side effects that are normally associated with BRAF inhibition.

Dr. Michael Rotkowitz, from Cancer Treatment Centers of America, on the Dabrafenib Plus Trametinib Combination for Melanoma

Michael Rotkowitz, MD

Articles

Dr. Rotkowitz Describes Challenges Facing Immunotherapy

Dr. Rotkowitz on Ipilimumab Plus Dacarbazine for Melanoma

Dr. Rotkowitz Defines Personalized Medicine

Dr. Rotkowitz on BRAF/MEK Combination Side Effects

Dr. Rotkowitz on the Dabrafenib/Trametinib Combination