ASCO Preview – Zytiga, T-DM1 among main draws at cancer conference

With the runners and riders revealed for this year’s Asco cancer conference amid another bumper crop of crucial data, the twin highlights of the conference look to be the detailed performance of Johnson & Johnson’s Zytiga in chemotherapy naïve prostate cancer patients and Roche’s breast cancer antibody conjugate T-DM1, in the Emilia study. Both results will have important implications for other drugs in the space.

Unlike previous years that have been dominated by groundbreaking melanoma data there are no real themes to 2012’s conference, but plenty of interest will be generated as ever by the late breaking sessions. As well as the Zytiga data this year they include Onyx Pharmaceuticals and Bayer’s GIST drug regorafenib and GlaxoSmithKline’s dabrafenib in melanoma.

Plenary Session

Demonstrating the interest that it has generated among cancer specialists T-DM1 has bagged one of the coveted plenary spots on Sunday June 3. Based on Herceptin with a cytotoxic agent attached, hopes are that the drug, one of the new wave of antibody drug conjugates, will prove much more potent than Herceptin alone (Therapeutic focus - Antibody drug conjugates still making slow progress, July 15, 2011).

Detailed trial data will be revealed from the Emilia study, which looked at 991 women already treated with Herceptin and then either given T-DM1 or a combination of Tykerb and chemotherapy drug Xeloda. Observers will be watching disease progression and more importantly on how the drug fares on the gold standard of overall survival. Roche itself is confident of the drug’s efficacy and has announced plans for a US filing by the end of the year.

Poised to share in any success of T-DM1 is ImmunoGen, which first developed the antibody conjugate; it is in line for mid-single digit royalties from any subsequent sales. Analysts current have sales of $970m for the drug by 2018.

Late Breakers

Among other results that are being kept a firm secret until the day of the presentation is Onyx Pharmaceuticals and Bayer’s regorafenib.

Bayer earlier his year presented data in colon cancer, where it showed an increase in overall survival time of six weeks, but the real interest is how the multi-kinase inhibitor performed in 199 patients with metastatic and inoperable gastrointestinal stromal tumours (GIST) whose disease had progressed despite prior treatment with imatinib and sunitinib.

Details released in March showed the trial met its primary endpoint of statistically significant improvement in progression-free survival, but what observers will be looking for are the finer details of the trial.

Among the other late breakers is GlaxoSmithKline’s dabrafenib. Now in its second year at Asco, the BRAF kinase inhibitor, in 2011 drew considerable interest last year in melanoma (ASCO – Melanoma hopes lie in combination approaches, June 6, 2011). The drug is back this year reporting phase III results that pit the drug against chemotherapy agent dacarbazine.

In the spotlight

While T-DM1 may have taken the plenary spot, the other big draw for this year will be the embargoed phase III data for J&J’s Zytiga. The drug was approved last year in men who had already failed chemotherapy, but this phase III study will look at how it performs in men in much earlier stages of the disease.

Signs are already looking good that Zytiga, an oral drug, could be a game changer in this space. A phase III trial was stopped early back in March on the advice of an independent data monitoring committee, after an interim analysis revealed a significant improvement in progression free survival in the Zytiga arm. Placebo patients were then given the drug.

While giving the placebo arm of the trial of Zytiga might cloud the data for overall survival, doctors and investors will be keen to determine if any survival benefit is evident in the full data.

J&J already scored a hit with an abstract of a phase II trial of pre-chemo patients, in which the drug eliminated or nearly eliminated signs of cancer in men with localized high-risk prostate cancer. The finding is likely to have contributed to weakness in shares of prostate cancer rivals Dendreon and Medivation today.

Give that analysts estimate there are twice the number of pre-chemotherapy prostate cancer patients than post-chemotherapy patients, Zytiga with its easy manufacturing and route of administration could threaten Provenge's patient pool.

The other contender

The post-chemo space in prostate cancer is also looking a lot more exciting with the advent of Medivation's MDV3100. In November, the group also had its 1,119 patient trial stopped early thanks to a clear survival benefit (Medivation roars back to life as prostate cancer drug delivers, November 03, 2011) .

Medivation will be reporting full data at Asco from the trial, which showed a median survival of 4.8 months over placebo - 18.4 months versus 13.6 months. The results were even better than Zytiga in the same setting, which initially reported a 3.9 month survival benefit, that increased to 4.6 months in a later analysis.

The drug could be big hit in the space given that it is used as a monotherapy. Zytiga is usually taken in combination with prednisone, but some doctors have started to speculate that steroid use could be behind the failure of later stage prostate drugs. Additionally, the side effects of prednisone make it difficult to manage.

Supporting acts

It has to be remembered that despite all the pom-pom waving not all Asco data is positive. After unveiling statistically significant but weaker-than-hoped for results for kidney cancer drug tivozanib - 11.9 months of progression free survival versus 9.1 months for Nexavar - Aveo will be heavily touting the drug's safety and tolerability, which it hopes will allow it to compete with the market incumbents.

While Aveo is looking to carve out share in a tight market, Seattle Genetics is looking to expand its. Adcetris is already approved in second line Hodgkins and anaplastic large cell lymphoma (ALCL) and with several pieces of data on display at Asco, Seattle is hoping to widen out the use of the drug.

Data from a phase II study of patients who were retreated with the drug following relapse confirms that Adcetris can be used multiple times in Hodgkin’s and ALCL. Out of the 14 Hodgkin’s patients who re-took the drug three went into complete remission. The results in ALCL were even better with five out of eight patients showing complete remission. 

Seattle will be hoping these results will increase use of Adcetris. However there have been safety issues with the drug, which now carries a black box warning on its label highlighting the risk of the rare but deadly brain infection PML. Despite this the real goal for Adcetris, which works by attaching itself to receptors on tumours that express the CD30 protein, will be expanding its use into solid tumours.

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