Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘ASCO 2014 Melanoma’

Today’s post focuses on another question from a reader, who asked: “How will we decide which therapies to give patients with metastatic melanoma once the new immunotherapies are available?”

This is not an easy question to answer, but first let’s remember that as little as five years ago there were only treatments such as DTIC (dacarbazine), temozolamide, interferon, chemotherapy and not much else as choices for people with advanced melanoma. Survival rates were generally poor, yet despite the low barrier to entry, many agents failed miserably to beat them. The disease was therefore widely considered to be a graveyard for Pharma R&D.

Fast forward to 2014. We now have several targeted therapies and combinations approved including BRAFV600E (vemurafenib and dabrafenib) and MEK inhibitors (trametinib), as well as a number of others that may soon be on the way in the near term such as cobimetinib in combination with vemurafenib.  Along similar lines, GSK recently announced that the combination of dabrafenib plus trametinib was superior to vemurafenib alone in terms of overall survival.  Hopefully, we will see the full data for both combinations at a medical meeting such as ESMO or EADO in the Fall.

Immunotherapies such as ipilimumab (Yervoy) have also been shown to improve patient outcomes. In addition, others are also in the queue including anti-PD–1 antibodies, which are likely to be reviewed soon by the Health Authorities (e.g. pembrolizumab and nivolumab). Indeed, Japan already approved nivolumab (Opdivo) in advanced melanoma on July 4th, making it the first anti-PD–1 checkpoint inhibitor to be available globally. Meanwhile, in the US Merck had a jump start with their rolling NDA for pembrolizumab already started (the PDUFA is Oct 28th, 2014). Their data at ASCO included probably one of the largest trials I’ve seen in advanced melanoma with over 400 patients included. BMS are not far behind with nivolumab, however, and are expecting to begin their filing in the 3Q this year following the frontline trial (CHECKMATE 037) in BRAF wild type (wt) metastatic melanoma versus dacarbazine successfully meeting its primary endpoint earlier than expected.

You can read about the clinical results relating to the three key melanoma trials reported at ASCO by Ribas et al., Hodi et al., and Sznol et al., in our earlier review but today, I wanted to focus on a broader, more strategic perspective, now that several events post meeting are shaking out more clearly.

A couple of years ago (was it really that long?!), many of us were quite disappointed to see the combination of vemurafenib plus ipilimumab scuttled due to unexpected liver toxicity, although the good news from ASCO is that a dual immunotherapy combination (ipilimumab plus nivolumab) appears not to have met the same fate.

The landscape for metastatic melanoma is therefore rapidly changing, but where is this field likely to go and what can we expect to see?

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Melanoma oral abstracts at ASCO 2014The melanoma oral abstracts session at ASCO 2014 was packed as a full house in the Arie Crown lecture theatre listened to the latest on new immuno-oncology therapies that are leading a revolution in melanoma treatment.

In the Clinical Science Symposium on PD-1 blockade and in the oral session at ASCO 2013 we heard how PD-1 antibodies nivolumab, MK-3475 (now pembrolizumab) and the PD-L1 antibody MPDL3280A had high response rates, long durations of response with favourable toxicity. This led to melanoma suddenly becoming one of the hottest areas of cancer drug development.

Global incidence of stage III melanoma continues to rise, with a high 5 year relapse rate (89% in stage IIIc), so there remains a need for more effective treatment options. It’s particularly sad to see so many young people end up with metastatic melanoma from over-exposure to tanning beds or too much sun! After going to several melanoma sessions, I don’t go out as much in the mid-day sun here in Florida.

So what did latest data show at ASCO 2014? Is pembrolizumab better than nivolumab? Will combinations be more effective than single agent therapies alone and will toxicities impact the risk:benefit profile?

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Chicago – it’s day 4 of the ASCO (American Society of Clinical Oncology) annual meeting. Sunday at ASCO can be a bit hit or miss depending on whether the plenary selection committee makes a good choice in which studies to give the “glory” and how interesting they are. It’s certainly been a busy meeting, although I have to say going round the poster halls has been a horrible experience.

For the first time this year, they doubled up the trials in progress posters, which makes it like a rugby scrum to reach the QR code to get a copy, and all it means is that people use smaller text to cram the same material into a smaller area. People do want to talk people about what’s going on, the rational for trials and it must be a miserable experience for presenters to be faced with such cramped conditions. Memo to ASCO – it was not a good idea and the new poster numbering layout is really hard to follow. It’s not as if there is a shortage of space.

Yesterday afternoon was an afternoon of plenary data. It was interesting to see leading breast cancer physician and influential ASCO member Robert Miller (@RSM2800) question the choice on Twitter:

While I completely agree with the need to publish negative data so that researchers in the field can better understand what happened and learn how to design trials better or differently, that is after all what science is about, I do question whether EVERYONE at ASCO needs to know that. An oral presentation of the ALTTO trial data in a breast cancer session would have been sufficient to achieve that goal. I personally thought the PREVAIL trial data from enzalatumide in advanced prostate cancer prior to chemotherapy was more worthy of plenary recognition than a negative data breast cancer trial. The PREVAIL data was published in the New England Journal of Medicine yesterday.

There were other data worthy of plenary recognition and we’ll be writing them up on the blog. So what’s on the agenda for today?  Subscribers can login below to read more.

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