Article and data regarding results of Pazopanib treatment

[Bonni Hess]

Dear ASPS Community Friends,
The following is an article regarding the results of Pazopanib treatment for Sarcoma patients that was posted in the September issue of the ESUN newsletter which is the electronic newsletter that I receive from the Liddy Shriver Sarcoma Initiative Foundation. Unfortunately, the data and conclusion provided in this article indicate that Pazopanib only provides a very modest benefit of three months progression free survival (PFS) for Sarcoma patients being treated with it. It is my greatest Hope that those ASPS patients who are currently receiving Pazopanib treatment will have a much more successful and significantly longer sustained response and PFS then indicated in this article, but I thought that this is important information to be aware of for all of those who are closely following and considering treatment with this new drug.
With special caring thoughts and continued Hope,
Bonni

Pazopanib in sarcomas: expanding the PALETTE

After failure of standard therapy, few effective treatment options exist for adult patients with metastatic sarcomas, and median survival remains dismal at approximately 1 year. Pazopanib, a multitargeted tyrosine kinase inhibitor, has recently been approved for nonadipocytic soft tissue sarcomas refractory to chemotherapy. In this review article, the authors revisit the efficacy of pazopanib in sarcomas, and present a patient case that illustrates two of many unanswered questions: which sarcoma patients are most likely to benefit from pazopanib therapy, and what criteria are best suited to accurately detect benefit in clinical trials? Recent findings: Pazopanib has been tested in sarcoma patients in a phase II and phase III study, and was shown to prolong progression-free survival by 3 months relative to placebo. Although histology has been the primary stratification variable for subgroup analysis in large sarcoma trials, the PALETTE study did not demonstrate superior response within histologic cohorts. Ongoing trials seek to explore efficacy of pazopanib in previously excluded histologies, as well as include correlative studies to identify histologic and molecular biomarkers to predict patients likely to benefit. Summary: Pazopanib has been proven to provide modest benefit overall to nonadipocytic soft tissue sarcoma patients, but we have yet to identify the molecular basis for those patients who derive exceptional benefit.

[Bonni Hess]

Dear ASPS Community Friends,
The following article was posted in the May 2014 issue of the Liddy Shriver Foundation ESUN newsletter regarding the results of Pazopanib (aka Votrient) treatment for Sarcoma patients who have been/are being treated with this drug. I Hope that this information is helpful for those of you who are considering systemic treatment with Pazopanib. It is important/of interest to note that the conclusion of the article states "Good performance status, low/intermediate grade of the primary tumor and a normal hemoglobin level at baseline were advantageous for long-term outcome".
With special caring thoughts and continued Hope,
Bonni
Long-term responders and survivors on pazopanib for advanced STS
Pazopanib recently received approval for the treatment of certain soft tissue sarcoma (STS) subtypes. The authors conducted a retrospective analysis on pooled data from two EORTC trials on pazopanib in STS in order to characterize long-term responders and survivors. Selected patients were treated with pazopanib in phase II (n = 118) and phase III study (PALETTE) (n = 226). Combined median progression-free survival (PFS) was 4.4 months; the median overall survival (OS) was 11.7 months. Thirty-six percent of patients had a PFS ≥ 6 months and were defined as long-term responders; 34% of patients survived ≥18 months, defined as long-term survivors. Patient characteristics were studied for their association with long-term outcomes. Results were as follows: The median follow-up was 2.3 years. Patient characteristics were compared among four subgroups based on short-/long-term PFS and OS, respectively. Seventy-six patients (22.1%) were both long-term responders and long-term survivors. The analysis confirmed the importance of known prognostic factors in metastatic STS patients treated with systemic treatment, such as performance status and tumor grading, and additionally hemoglobin at baseline as new prognostic factor. They identified 12 patients (3.5%) remaining on pazopanib for more than 2 years: nine aged younger than 50 years, nine females, four with smooth muscle tumors and nine with low or intermediate grade tumors at initial diagnosis. The median time on pazopanib in these patients was 2.4 years with the longest duration of 3.7 years. Conclusions: Thirty-six percent and 34% of all STS patients who received pazopanib in these studies had a long PFS and/or OS, respectively. For more than 2 years, 3.5% of patients remained progression free under pazopanib. Good performance status, low/intermediate grade of the primary tumor and a normal hemoglobin level at baseline were advantageous for long-term outcome

[D.ap]

Hello Bonni

I would venture to say that the surgical removal of tumors even in the stage IV of ASPS is still the consensus?
If need be to shrink the tumor ,maybe plazopanib could be used to shrink then radiate ,as in Kevin and Connie's situation on the spine base and any other area that was deemed too big to surgically remove till reduced to a manageable size to receive good margarines
removal ?

The link tells of sarcoma treatments in stages and how surgery and chemo are sometimes combined .
I agree that by itself pazo doesn't appear to do a lot of good for a sarcoma like ASPS

http://m.cancer.org/cancer/sarcoma-adul ... g-by-stage
Comments welcome

Love
Debbie

[Bonni Hess]

Dear Debbie,
Yes, based on my knowledge from almost 13 years of personal experience with Brittany's very challenging ASPS battle combined with extensive research, observations, and networking, I think that surgical removal (resection) of tumors if possible remains the most effective treatment for ASPS, and if surgical removal is not possible, shrinkage/destruction of the tumors with ablation or radiotherapy is the next best treatment. It seems that systemic treatments like Pazopanib have a more successful response when the tumor burden has been reduced as much as possible with resection, ablation, or radiotherapy. Because ASPS is so radiation resistant, standard radiation does not seem to be very effective in shrinking/destroying ASPS tumors. Unfortunately, resection, ablation, or radiotherapy are not always treatment options for some ASPS tumors which are located in dangerous /difficult to access areas of the body as was the case five years ago with Brittany's unresectable, untreatable, Life threatening pancreatic met which was located at the head of her pancreas. Thankfully, Cediranib appears of have been successful in shrinking and destroying the pancreatic met in addition to all of Brittany's scan visible innumerous and widely disseminated mets. Sadly, I have not personally observed a very significant or sustained successful response to Pazopanib for those patients who I closely follow who are taking/have taken Pazopanib. The article which I shared seems to support this observation and conclusion with the combined data from Phase 2 and Phase 3 Pazopanib Trials which showed that the combination study results for Pazopanib patients in the two Trials was only "Combined median progression-free survival (PFS) was 4.4 months; the median overall survival (OS) was 11.7 months". It is encouraging that "For more than 2 years, 3.5% of patients remained progression free under pazopanib", however it seems that 3.5 % is a very small percentange in terms of overall success of the drug for the majority of the patients.
The critical need for a more effective and sustained systemic ASPS treatment remains, and the aggressive and relentless search must continue through shared anecdotal treatment information and ongoing research.
With special caring thoughts and continued Hope,
Bonni

[Johannes]

Dear Bonnie,

My impression is that Pazopanib alone cannot be very effective in the long run. Unfortunately, there is very little data available with respect to combinations (and there are apparently not many studies going on), but are a few cases where resistance to Pazopanib could be overcome by adding an mTOR inhibitor (to a lower dose of Pazopanib). I understand that two drugs can sometimes produce pretty bad side effects, but my feeling is that many oncologists just want to play it safe and are too reluctant to try things... anyway, these are just a few more thoughts on these certainly not very encouraging publications.

Johannes

[D.ap]

Dear all
Found this abstract in the ASCO meeting papers submitted, which I found interesting. Using PET to veiw early on possible success of pazonib, in sarcoma patients .



Early metabolic response as predictor for treatment outcome of pazopanib in patients with metastatic soft tissue sarcomas (the PREDICT study).

https://meetinglibrary.asco.org/record/162375/abstract

Johannes,
I’d be interested to hear of any updates you’ve heard of in combinding lower doses with mTOR inhibitor as well.
Elisa was on pazonib for 2 years?


Sincerely
Debbie