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MD-FM with the Audio Journal of Oncology, Tuesday May 21st, 2013

 

GENERIQUE

Carillon

 

Sarah:

The Audio Journal of Oncology with MD FM: in this edition we report from the American Association for Cancer Research Annual meeting held in Washington DC. Here’s Peter Goodwin.

 

P1 Jack Cuzick

Breast cancer chemoprevention: meta-analysis shows SERMs are highly effective

PETER:

Hello. And with me is Sarah Maxwell.

New research has shown that you can prevent breast cancer by treating patients at high risk with selective oestrogen receptor modulators, SERMS.

 

SARAH:

Yes. Although there’s already evidence that one of these, tamoxifen, can do this, it hasn’t been widely used. Now, however, a meta-analysis in the Lancet has added new data from studies of four SERMS: tamoxifen, raloxifene, ar-zoxifene, and layzo-foxifene; and this all brings compelling evidence that millions of women could be spared this terrible disease…

 

JACK CUZICK

Basically what we’ve done is we’ve identified all of the trials that have looked at a SERM, in a way that had a breast cancer endpoint, gone back got all the individual data, updated the follow-up so for example for the Tamoxifen trials we have ten years and longer follow-up, and we’ve basically put all of this data together to look at the overall effect of SERMS during treatment and importantly to try to determine how long the benefit lasts. The data are very very clear, the early results of prevention of breast cancer were maintained although there was a 38% reduction of all breast cancers, it’s about 50% for ER-positive breast cancers. And the important new data is that this is sustained in the five years after treatment, the effect size is not quite so big in those five years, but it carries on and its still important to find out what happens in years ten to 15, because if this benefit continues even longer, the benefits are going to continue to improve and the side effects have disappeared after you’ve stopped treatment 

 

SARAH:

That was lead author of the Lancet article, Professor Jack Cuzick from Queen Mary, University of London who was reassuring about the potential toxicities of using SERMS long-term despite worries voiced in the past about: endometrial cancer and thrombo-embolic risk:

 

JACK CUZICK 02

Those are very clear and real side effects, the thromboembolic risk is only there while your taking the drug, once you stop taking the drug, the effect disappears. Endometrial cancer is a bit more mixed, in the trials we’ve seen no excess of endometrial cancer after the five year treatment period but other data suggests that there probably will be some coming through, we just haven’t seen them, but it’s a very very small factor compared to the reduction of breast cancer 

 

SARAH:

Jack Cuzick from the Wolfson Institute for Preventive Medicine at Queen Mary, University of London.

 

VIRGULE MUSICALE

 

P2 Lana Kandalaft

Two-step immunotherapy brings promise in advanced ovarian cancer

 

  

PETER:

Refractory ovarian cancer could potentially be treated successfully with a two stage immunotherapy treatment — according to study findings presented to the 2013 American Association for Cancer Research annual conference in Washington DC.

 

SARAH:

Dr Lana Kandalaft from Philadelphia and her colleagues have combined dendritic cell vaccination with adoptive T-cell therapy: first using an individualised vaccine prepared from the patients’ own tumours to stimulate immune defences against the cancer, and then T-cell therapy:

 

Lana Kandalaft 01

Our results are preliminary but very encouraging, so we have treated 31 patients, out of those 31 patients we had 20 who had clinical benefit, so 20 who have responded. Meaning they have not progressed and you have to keep in mind this is a recurrent ovarian cancer population, where there’s really no drugs to treat this disease. And that’s after vaccination. After we vaccinate them, we take them now into an adoptive T-cell therapy trial, and what we do is we collect the vaccine prime T-cells from those patients and then we infuse them again after we expand them and activate them. And here we treated 11 patients, seven of which had clinical benefit, one of which actually had a complete response. 

 

SARAH:

Dr Kandalaft says that such a labour-intensive approach may not catch on overnight but it’s not rocket science and it produced very real benefits in patients with no other options:

 

Lana Kandalaft 02

It’s telling us that immunotherapy could have a potential in prolonging time to progressionin patients with recurrent ovarian cancer. In our case some patients have never recurred, some of them have stable disease which have not progressed, which probably it’s standard of care would have progressed by now 

 

SARAH:

Lana Kandalaft from the University of Pennsylvania in Philadelphia, talking to us in Washington DC.


 

VIRGULE MUSICALE

 

P3 Daniel Lee

Chimeric antigen receptor T-cell therapy rescues kids with relapsing acute lymphoblastic leukaemia

 

PETER:

You’re listening to the Audio Journal of Oncology with Sarah Maxwell and me, Peter Goodwin, reporting from the 2013 AACR conference.

And we continue with: chimeric antigen receptor or, CAR, T-cell therapy. It involves modifying cells from the patient’s own body.

 

SARAH

Three children with relapsing acute lymphoblastic leukaemia, who’d run out of treatment options — had remissions of their cancer with this new form of immunotherapy. Dr Daniel Lee:

 

Daniel Lee:  01

Of our four patients, three had ALL, or acute lymphocytic leukemia, one patient had a B-cell lymphoma. Three of those patients previously had bone marrow transplants, and it replapsed with their disease after that transplant. And in two patients we had striking responses, or complete responses in fact, one of those patients went on to relapse unfortunately a few months later, but one of those other patients who had never had a bone marrow transplant, and who had been completely resistant to multiple rounds of standard chemotherapy, developed a complete remission good enough to get her to a bone marrow transplant which hopefully will be curative in her 

 

SARAH

Daniel Lee, from the Pediatric Oncology branch of the National Cancer Institute in Bethesda, Maryland, who told us this is not ready for prime time, but brings new hope.


 

VIRGULE MUSICALE

 

P4 George Demetri

Blood test reliably detects cancer mutations in patients with gastrointestinal stromal tumor (GIST)

 

 PETER:

Treatments for gastrointestinal stromal tumour, or GIST, could be improved with the help of a new blood test that’s reliably detected mutations for drug resistance.

 

SARAH:

Yes. It’s all about looking for mutation-driven kinases that drive GIST, according to Dr George Demetri. He told us you can miss mutations with conventional biopsies because tumours are hetero-geneous, hence the need for the new test called: BEAMing

 

George Demetri 1

BEAMing is an acronym that stands for: Beads, Emulsion, Amplification and Magnets, and it’s a technology that grew out of Bert Voglestiens lab at Johns’ Hopkins then got taken up by a German company called Inostics. What they’re looking for is a way of amplifying mutated DNA that’s just floating around free in the bloodstream. Now remember in GIST, many of the patients who are multiply resistant to kinase inhibitors, have a lot of disease, have kilograms and kilograms of tumours. So those tumours are constantly dying and apoptosing in the patient and they’re liberating bits of mutated DNA. So this is a population where we said we should be able to find a lot of the mutant DNA in the bloodstream. But how do we amplify it, how do we understand it? This technology seemed perfect. So while we were developing this study that would test the worth of this new kinase inhibitor regorafinib, with the study sponsor there, there was very willing to pay for some of the correlative science and contract with Inostics and do this testing on the bloodstream of patients in the definitive phase III trial 

 

SARAH:

The phase three GRID study, using rego-rafinib, included an evaluation of this BEAMING method:

 

George Demetri 2

What we found is that a lot of our patients could easily have the resistance mutations detected in the bloodstream. We were able to detect at least 50 / 47% of the patients with resistance mutations, sometimes even double mutations in the bloodstream, whereas by looking at the tumour samples, the paraffin fixed tumour samples, it was only about ten to 12% of patients could we detect the resistance mutations 

 

SARAH:

George Demetri, from the Dana-Farber Harvard Cancer Center in Boston.


 

VIRGULE MUSICALE

 

P5 Geoffrey Shapiro  

BRCA-deficient cancers respond to combination of two experimental drugs


 

PETER:

It’s not often in clinical trials that two experimental drugs are used simultaneously, but the AACR meeting heard that this was justified in a group of patients with BRCA-associated cancers:

 

SARAH:

Yes, apparently BRACKA can indicate potential response to the drug combination used. Dr Geoffrey Shapiro told us why they combined sapa-citabine and selecyclib:

 

Geoffrey Shapiro 1

This was two experimental agents, the first was sapacitabine which is a type of chemotherapy in the sense that it is a DNA based analogue and will be incorporated into growing DNA chains. But it is a very well tolerated drug that is being looked at, right now both in leukaemia and lung cancer. Our initial thoughts on the trial is how are we going to make sapacitabine work better? And there were quite a bit of data that suggested that the addition of a class of agent called a CDK inhibitor a cycle independent kinase inhibitor would do that. And this is data dating back many years on the cycle independent kinases that comes from many groups that suggests that agent such as sapacitabine can be augmented in their activity by adding the by adding a CDK inhibitor 

 

SARAH:

These two drugs target homologous recombination which is one of the cancer cell’s repair processes.

Breast and ovarian cells which are naturally BRACKA deficient, were expected to be hypersensitive to this therapy. The study found a good response in a patient with pancreatic cancer that was BRACKA deficient, and then more successes:

 

Geoffrey Shapiro 2

And now out of those 16 total with BRCA deficiency, we’ve had fairly striking results in six of them. So four of them have actually had very very nice shrinkage of the tumour, three others in addition to this pancreatic cancer patient, two breast cancer patient and one ovarian cancer patient, as I mentioned one of the breast cancer patients, the response is almost complete and has lasted almost 20 months. And the other breast cancer patient and the ovarian cancer patient are not far behind in the length of time that those responses have remained. And two other patients have had very prolonged stable disease, one of them well over a year. And so those six patients have derived very significant clinical benefit out of the combination 

 

SARAH:

Geoff Shapiro, Director of the Early Drug Development Center at the Dana-Farber Cancer Institute in Boston. He thought this was proof of principle that mechanisms like homologous recombination can be targeted.

 

PETER:

 

And finally:

 

B1

 

PETER:

Gene expression and molecular pathways could soon guide therapies for head and neck cancer. Researchers from North Carolina investigated common mutations and copy number alterations in samples from 300 patients and checked their findings with reference to the Cancer Genome Atlas. They found that at least half the patients had theoretically targetable mutations; and there were pathways that hold therapeutic potential, among them tyrosine kinases bringing more therapy options.

 

And…..

 

B2

 

PETER:

Treatment “holidays” could help overcome resistance to cancer drugs in advanced melanoma according to another study presented to the AACR. Research in mice using the drug vemurafenib, and also anecdotal clinical reports, has shown that pausing treatment could improve outcomes, since continuous treatment runs the risk of selecting cancer cells for drug resistant phenotypes

That's all from the Audio Journal of Oncology with MDFM reporting from the American Association for Cancer Research annual meeting. We’ll be back with more cancer news, soon, until then, from Sarah Maxwell and, from me Peter Goodwin, goodbye!

JINGLE FIN  

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