Update on experimental CLL and NHL drug – idelalisib

July 4th, 2014

Gilead Sciences continues to invest in the drug originally known as CAL-101 and now known as idelalisib. Gilead acquired this drug along with the rest of Calistoga Pharmaceuticals back in 2011. Clinical trial data for both CLL and non-Hodgkin’s lymphoma look good, and the FDA is scheduled to complete a priority review of Gilead’s New Drug Application for CLL by early August and for NHL by early September.

There are 11 clinical trials currently open and recruiting new patients. Importantly (and congratulations to Gilead for doing the right thing!) there is an expanded access program for patients with relapsed, previously-treated CLL who are not eligible for other Gilead clinical trials. The expanded access protocol provides for idelalisib to be used in combination with rituximab.

Although for some patients, diarrhea is a serious side effect, for many people it is not severe and can be controlled with other medication. In general, this is a much milder drug than many options that people with cancer must choose from, and the efficacy results some patients have experienced is quite dramatic.

Of note is a mouse study recently published in the scientific journal “Nature.” It turns out that, in mice at least, this drug works rather well against solid tumors.  Earlier in the drug’s development, the expectation was that it would be limited to use primarily against leukemias and lymphomas rather than solid tumors. It will be a while before human clinical trials test the usefulness of this new drug against solid tumors, but it’s certainly worth watching and keeping in mind as more data become available.

A Lymphoma and CLL Experimental Drug to Watch

February 26th, 2013

Cal-101, now called GS-1101, is an oral drug (technically a PK13-delta inhibitor) developed by Calistoga Pharmaceuticals showing great promise for the treatment of certain non-Hodgkin’s lymphomas and chronic lymphocytic leukemias. Calistoga was taken over by Gilead Sciences which is now advancing the experimental drug through Phase 3 clinical trials.

We have heard very positive things about the performance of GS-1101. Unfortunately, Gilead did not respond to our request for additional non-confidential information, so we will do other research and post additional perspectives here as we are able. There are a number of clinical trials open for enrollment, and you can do a little research on your own at the NCI’s clinical trials site: http://www.cancer.gov/clinicaltrials/search/results?protocolsearchid=11431626

WHO Links Cell Phone Use to Possible Increased Cancer Risk

May 31st, 2011

The World Health Organization released an announcement today linking cell phone use to a possible increased risk for glioma, a malignant brain cancer.  Possibly more significant is evidence that low level cell phone radiation may increase the risk of damage to brain tissue (in the same way that microwaves cook meat), resulting in impairment of some neurological functions.

The mobile phone industry is certain to reject WHO’s findings due to their overwhelming financial interest in having the link not be credible. There are sure to be claims and counter-claims in the coming years over the interpretation of the statistical data WHO used to reach their conclusions, and there will undoubtedly be political debates over the question of regulation of cell phones from a public health standpoint. The WHO press release can be found at this link: WHO cell phone cancer risk.

While the WHO study does not claim proof of a cause – effect relationship between cell phone use and glioma or other brain health issues, everyone deserves access to as much detailed information as possible to make an informed personal choice, even when the evidence is not yet definitive.

Experts weigh in on PFS and OS

August 4th, 2010

Although living without disease progression is clearly a good thing, in the ongoing debate over the use of progression-free survival (PFS) as a formal endpoint in clinical trials, one frequent concern is how does PFS relate to overall survival (OS) or extension of life. As a follow-up to our earlier post, we thought you might be interested in seeing what some of the experts have to say. The following link will take you to a summary of a paper published in late 2009 in the Journal of the National Cancer Institute in which leading statisticians analyze the relationship between PFS and OS in the context of how long a person is likely to survive after disease progression, something that varies substantially among different cancer types and stages.

JNCI December 2009

Although there are many aspects to consider in the PFS versus OS debate, one of our concerns is that by discounting a significant increase in PFS when it is not acccompanied by a statistically significant increase in OS, we might be rushing to judgement and missing important clinical benefits for some patients provided by a treatment that does not work for every patient.

Clearly, better tools are needed to predict which patients will benefit and which will not benefit from any given treatment (and importantly, which will be harmed), but that is a topic for another post. . .

When is Progression-Free Survival an Important Clinical Trial Endpoint?

August 2nd, 2010

We all hope for breakthroughs in the treatment of cancer and for a substantial improvement in the experience many people go through after a diagnosis of cancer. Unfortunately, experience teaches us to value incremental progress at the same time we work for more substantive progress. An issue of importance in current clinical cancer research is how best to measure progress without delaying the transfer of improved treatments from the research center to general availability to all patients who might benefit. 

One way to speed progress might be to use clinical trial endpoints that suggest treatment value without actually proving life extension.  An endpoint that we believe to represent real clinical benefit to patients is called “progression-free survival.” This is a measure of how long a person lives without a detectable growth of cancer. Unfortunately, even when a clinical trial demonstrates that a new treatment increases progression-free survival, it doesn’t always result in a prolongation of life. This could be because the new treatment doesn’t provide much benefit; it could be because other treatments are successful enough to make detection of life extension difficult, or it could be that the treatment works for a minority of patients and does nothing for the majority, thus hiding a benefit for some in the disappointing outcome for many. 

A recent example of public debate on the relative importance of progression-free survival versus overall survival as an endpoint in clinical trials was the July meeting of the FDA’s Oncologic Drugs Advisory Committee which reviewed data on the use of Avastin (bevacizumab) for the first-line treatment of metastatic breast cancer. The committee voted to recommend removal of breast cancer from the FDA approved use of Avastin, and the FDA will make a final decision sometime in the next several weeks.  Our position is that despite the disappointing lack of evidence of a significant improvement in overall survival, treatment with Avastin should continue to be an option for women with metastatic breast cancer. This is because we believe some women receive a significant benefit even though for others the drug is ineffective. We think a patient and physician together should be able to make an informed choice about whether or not to use this treatment. You can read a copy of our letter presented at the ODAC meeting which is posted on our website here: MNCF July 2010 ODAC Comments.

We encourage discussion on the topic of progression-free survival as a clinical trial endpoint. Whether you agree with our position or disagree, we would like know what you are thinking and to share your views with others. Please consider writing a comment on this important topic.