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Combination immuno-blockade is a potential breakthrough for melanoma and cancer treatment

 MD-FM Thursday June 6, 2013 





GENERIQUE

Carillon

 

Sarah:

MD FM — Medical News from around the world with Peter Goodwin.



P1

PETER:

Hello, and with me is Sarah Maxwell. To begin with, news direct from the annual meeting of the American Society of Clinical Oncology, which took place earlier this week in Chicago.

 

For patients with advanced, treatment-resistant melanoma, using a combination of two antibodies that target immune mechanisms could improve outcomes according to a study from New York...

 

SARAH:

Yes there were some exciting stories at ASCO about re-activating the body’s immune system to fight tumour cells by releasing so-called: checkpoint inhibition. And this study also combined this with an agent acting on T-cells.  So 53 patients were given a combination of ipilimumab, an anti-CTLA-4 agent, and nivolumab, a PD-1 receptor inhibitor, and half of them had an objective response with tumour reductions of 80% or more. Dr. Lynn Schuchter who was not involved in the study gave us her thoughts:

 

Schuchter: I have to say that investigators and physicians were concerned about combining PD-1 and “ipi”, that’s a very powerful way of shutting down the immune system. And these are very preliminary data, a relatively small number of patients treated, but really exciting results. So: higher response rates than what we’ve talked about, cautionary about the side effects but certainly manageable side effect 

 

SARAH:

That was panel commentator Lynn Schuchter, from the University of Pennsylvania, who agreed with the researchers that this new immunotherapy approach could herald a new treatment era for patients with melanoma. James Riley wrote an editorial on the study, published in the New England Journal of Medicine:

 

Riley: There’s certainly a tremendous unmet medical need in getting durable responses to these tumors. These two particular therapies target actually the host immune system rather than the tumor itself, so it has the potential to be a very durable therapy, because once the immune system becomes educated to the tumor, it should continue to try to fight it and to prevent relapse. One of the really nice thing about these therapies is that they are not limited to a specific tumor, they really could be used in a wide range of cancers 

 

SARAH:

Dr James Riley from Philadelphia.



VIRGULE MUSICALE



P2

PETER:

More news from ASCO, and for patients who had previously treated, advanced non–small-cell lung cancer with rearrangements of the anaplastic lymphoma kinase, or ALK, gene. The oral drug crizotinib, a tyrosine kinase inhibitor targeting ALK, was superior to standard chemotherapy in an open-label phase three study

 

SARAH:

Yes, median progression-free survival was more than doubled for patients on crizotinib compared to chemotherapy. And, there was a 65% overall response rate with crizotinib, compared to only 20% with chemotherapy.

 

PETER:

Hmmm, and how did side effects compare between the two groups?

 

SARAH:

Well crizotinib was associated with visual disorders, GI side effects and higher levels of liver enzymes. Lung cancer expert Suresh Ramalingam, from Atlanta, who didn’t participate in the study, gave us his reactions:

 

Ramalingam: If you take a step back you might recall that crizotinib was approved based on a single arm trial that included about 120-130 patients. There was no randomized comparison to see how it would compare to standard therapies. So this trial you are seeing, it confirms that crizotinib is better than standard therapy, in patients who have the ALK-translocation, that’s about 5 to 7 percent of all lung carcinomas, and it’s a therapy that’s tolerated well, and the median progression free survival is nearly 7 and a half months in the salvage setting, and perhaps even longer in patients who get it upfront. I think we now can say, for patients with ALK-positive non small lung cancer, ALK-inhibition with crizotinib is an excellent form of therapy and should be prefered for those patients 

 

SARAH:

That was Dr. Suresh Ramalingam speaking to MDFM in Chicago. And you can find the details of the study in this week’s edition of the New England Journal of Medicine.



P3

PETER:

And a final piece of news from the ASCO meeting: For patients with metastatic differentiated thyroid cancer who are resistant to standard radioactive iodine therapy, sorafenib reduced tumour progression in a randomised double-blind phase three study. The drug almost doubled progression-free survival, by five months, making sorafenib the first active agent in four decades in this disease.

 

VIRGULE MUSICALE

 

P4

PETER:

In last week’s edition of MDFM we reported that some statins appear to increase the risk of developing diabetes. And it now appears that statins are also associated with broader musculoskeletal problems than was previously thought

 

SARAH:

Yes, administrative data collected from the military healthcare system in the US showed statins were associated with a wide variety of conditions including: arthritis, muscle weakness, muscle cramps and tendon diseases. The study, published in JAMA Internal Medicine, compared around 7,000 statin users with about 7,000 non-users and Dr. Eric Mortensen was senior author of the study:

 

Emerson-1: This is actually a very healthy population overall but that were still on these medications. Under 20 percent were on the high potency ones, while over 70 percent were on simvastatin 

 

SARAH:

Eric Mortensen, who said that while the full spectrum of adverse events still needs to be explored, these data suggest that practitioners should think twice before putting young, healthy people with mildly elevated LDL levels on statins

 

Emerson-2: So really our main message is that physicians really need to follow the clinical practice guidelines for these medications. Use them for those for whom it is truly indicated in, those who need secondary prevention or who are at very high risk for cardiovascular diseases. They’re good medications but all medications have side effects and when the side effects are more likely than preventing the harm, this isn’t a good thing 

 

SARAH:

Eric Mortensen, from the University of Texas Southwestern Medical Center in Dallas.

 

 

VIRGULE MUSICALE

 

P5

PETER:

For patients with diabetes who are “moderately obese”, gastric bypass surgery improved disease treatment outcomes according to a study reported in JAMA

 

SARAH:

Yes, it was looking at patients with a BMI between 30 and 40. At one year, 49 per cent of patients who had Roux-en-Y gastric bypass on top of lifestyle and intensive medical management saw an improvement in their co-morbid risk factors, compared to just 19 per cent of those who didn’t get the surgery

 

PETER:

Sounds encouraging, but were there any side effects with surgery?

 

SARAH:

Well yes, there were definitely more adverse events. But Dr. Bruce Wolfe, who wrote an editorial on the study in JAMA, said that, besides one cerebrovascular event that occurred as a complication of surgery, side effects were relatively minor and managed successfully. However, longer follow up is needed to assess long-term safety and whether the overall health benefits of gastric bypass are maintained:

 

Wolfe: The classic indication for surgery is BMI 35 and above, and type 2 diabetes or other complications. Whether it should be extended to less severe obese remains to be seen, but I think it’s very encouraging and, in selected cases, particularly where the diabetes is difficult to control or in an environment where the medication and intense monitoring is not feasible, surgery is a reasonable to pursue. But a widespread recommendation is not quite ready to happen. We are also probably going to be getting away from BMI being quite so important in determining what treatment should be because it’s more complicated that just measuring the BMI 

 

SARAH:

Bruce Wolfe, from Oregon Health and Science University in Portland.



BREVE 1

 

PETER:

Finally, in brief: higher blood iron levels may protect against Parkinson's disease, according to a study reported in PLOS Medicine. For every 10 microgram per decilitre increase in blood iron, the authors found a 3% relative reduction in the risk of Parkinson´s disease. The underlying mechanism at play here, however, is still to be uncovered.

And...

 

BREVE 2

Prescriptions for testosterone therapy in the United States have tripled over the past 10 years, according to a report in JAMA Internal Medicine. The data show about half of men looked at were prescribed testosterone for hypogonadism. And sexual dysfunction was also a big reason. However, about 25 per cent of new users did not have their testosterone levels tested before starting therapy, and among those who did, it was unclear how many actually did have low levels of testosterone.

That's all from MDFM for now. Sarah Maxwell and I will be back with more next week, so until then from me Peter Goodwin, goodbye!

 

JINGLE FIN      

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