Nexavar (sorafenib) has been in a clinical trial for GIST that has now been completed, showing positive results for efectiveness in many patients who had developed resistance to imatinib and sunitinib. It has already been approved to treat kidney cancer (renal cell carcinoma). Some GIST patients have been prescribed Nexavar "off-label."
Bayer says that its FINANCIAL ASSISTANCE PROGRAM program for Nexavar (called the REACH program) does apply to any patient for whom is is prescribed, even for off-label use.
There is help from Bayer if you have QUESTIONS about Nexavar. It's called NexConnect. It's a 24 hour 7 day a week hotline staffed by oncology nurses. The number is 1-866-Nexavar ( 1 866-639-2827).
The NCCN Soft Tissue Sarcoma Guidelines version 2.2009 include sorafenib as a "generally accepted systemic therapy" for GIST (see page 35 of the 69-page pdf of the guidelines document, which is available after a free regisration at http://www.nccn.org ). The inclusion of sorafenib (Nexavar) in the NCCN guidelines may help patients obtain insurance coverage for off-label use.
I had problems with my feet when I was on Nexavar. Things were bad when I was on my feet for long lengths of time and then I end up off my feet for 2-3 days. What helps a little is wearing gel pads in your shoes and thick socks. With summer here, thick socks don't sound ideal, but they do help.
Nexavar hotline? The program is called REACH. There are two nurses who answer the phone lines and take questions and give good support and advice regarding Nexavar. The nurse I spoke with was so kind and spent probably an hour with me.
The number is 1-87-REACH-4-IT (1-877-322-4448) The phone line is available Monday through Friday 9 am to 8 pm EST.
The company will also provide a small backpack with lotion and cream to use for your feet. Perhaps you may have already received one when you were prescribed Nexavar.
Yes, the nurses at Nex-Connect are very caring and helpful.
Dear Gist Pals, Just reporting in my experience with Nexavar... Began at 400 mg on December 30,2010 then to 600 mg on January 6th. Severe pounding daily (or nightly) headaches started January 9th, followed by achey knees, sore mouth, eye blood bursts, and incredible chemo brain! Quit Nexavar on January 13th. If the side effects subside I will try Nexavar at 400.
Seems to me 400 should be the max dosage for anyone - at 800 I had a full body blistered rash and was a mess as well. Even at 400, my chemo brain often stops me in my tracks. Words just don't come to me and my kids have gotten very used to finishing my thoughts for me. I will say though, that it comes and goes and has subsided with time.
From Medscape Medical News > Oncology Sorafenib Effective in Resistant GIST Roxanne Nelson
January 20, 2011 — The multikinase inhibitor sorafenib (Nexavar) might be an effective option for patients with gastrointestinal stromal tumors (GIST) that have developed resistance to standard therapies.
The results of a small phase 2 trial have shown that sorafenib has activity in GIST patients who have stopped responding to both imatinib (Gleevec) and sunitinib (Sutent). The overall disease control rate with sunitinib in this population was 68%.
Of this group, 13% achieved a partial response and 55% had stable disease. Median progression-free survival was 5.2 months and overall survival was 11.6 months.
The results of this study will be presented at the 2011 Gastrointestinal Cancers Symposium (GICS) in San Francisco, California, and were highlighted ahead of time in a presscast organized by the American Society of Clinical Oncology, which cosponsored the meeting with a number of other societies.
GIST is the most common sarcoma of the gastrointestinal tract and is generally associated with the activation of KIT or PDGFRA gene mutations. Treatment has been revolutionized with the introduction of imatinib, which has yielded a control rate of 80%, explained lead author Nicholas P. Campbell, MD, an oncology fellow at the University of Chicago in Illinois.
Sunitinib has been approved for second-line treatment. It has a response rate of 7% and a median progression-free survival rate of 6.2 months, he explained.
However, Dr. Campbell said, "after failure on imatinib and sunitinib, there are limited therapeutic options."
Sorafenib has demonstrated both clinical and preclinical activity against resistant GIST, and inhibits KIT, VEGFR, PDGF, and BRAF kinases. It has also shown activity in a retrospective series of refractory GIST patients previously treated with imatinib, sunitinib, and nilotinib, Dr. Campbell said.
Activity Seen in Resistant Patients
The study was designed to evaluate the effectiveness of sorafenib in patients with unresectable KIT-expressing GIST who had disease progression despite treatment with imatinib. The study was amended in 2007 — after approval by the US Food and Drug Administration of sunitinib for patients resistant to imatinib — to require progression after both imatinib and sunitinib.
The participants were 6 patients who were resistant to imatinib only (from the initial cohort) and 32 who demonstrated resistance to both agents. The primary end point was objective response rate; secondary end points included toxicity, progression-free survival, and overall survival.
Patients received sorafenib 400 mg orally twice daily for a 28-day cycle, and computed tomography scans were performed every 2 cycles. The median follow-up for survivors was 31 months.
The study found 1 confirmed partial response in the group resistant to imatinib only (17%) and 4 in the group resistant to both imatinib and sunitinib (13%).
Median progression-free survival was 3.4 months in the group resistant to imatinib only and 5.2 months in the group resistant to both agents. Median overall survival was 13.6 months and 10.5 months, respectively.
Dose reductions were required in 63% of patients, primarily for hand-foot syndrome (45%) and hypertension (21%), which were the most common grade 3 toxicities, explained Dr. Campbell.
"These data demonstrate that sorafenib has definite activity in imatinib- and sunitinib-resistant GIST," he concluded. "Prolonged disease control is possible in these refractory patients, even those with primary sunitinib resistance. [National Comprehensive Cancer Network] guidelines now recommend sorafenib as an option for patients with imatinib- and sunitinib-resistant GIST."
ADVANCES IN TREATMENT:
Patients with metastatic GIST generally do well, and live approximately 4 years after diagnosis, said Jennifer Obel, MD, a medical oncologist at NorthShore University Health System in Chicago.
"Unfortunately, many patients have limited options at some point during their illness," said Dr. Obel, who moderated the presscast and was not involved in the study. "By understanding the molecular mechanisms behind GIST, we have been able to make great strides in our care of these patients."
"Over the past 10 years, 2 medications have been approved for GIST. This presentation demonstrates that additional treatments may be on the horizon because of our investment in clinical research such as this study," she added.
The study was supported by grants from the National Cancer Institute. Dr. Campbell has disclosed no relevant financial relationships. Several coauthors disclosed relationships with Bayer, Lilly, Novartis, ZIOPHARM Oncology, Pfizer, and Roche
2011 Gastrointestinal Cancers Symposium (GICS). Abstract 2. Presented January 20, 2011.
Roxanne Nelson, staff journalist for Medscape Oncology.