Pharma Strategy Blog

The challenge with ASCO is that it is now so big that you almost have to pick tracks by pathway or tumour type and limit yourself to picking out of the hat and hoping you pick more winners than losers >.<

One session that gave me goosebumps was the gastric cancer session last Monday. 

Dr Ajani reviewed a phase III trial that looked at the impact of neoadjuvant chemotherapy with 5FU/LV plus cisplatin versus surgery alone for locally advanced
adenocarcinoma of the stomach and cardia in an EORTC randomized trial (40954).  I notice now that no notes were written in my Moleskine other than the abstract/presenter and gist of the study.  Clearly I was waiting for a punchline that never came, because the CT showed no significant survival benefit in that patient population.

However, the data that made a packed audience sit up on their seats was the next presentation, where Eric van Cutsem described the data from the global EORTC ToGA trial.  They screened over 3800 patients to determine how many were HER2+, and of the 810 positive patients (22.1% HER2+), entered 584 into the ToGA trial.  This study looked at the impact of adding Herceptin (trastuzumab) to either capecitabine of 5FU in compbiation with cisplatin.  The primary endpoint was overall survival with the goal of increasing survival from 10 to 13 months.  97% patients in the study had metastatic disease, which is unfortunately common for the condition.

Here's what the overall data showed across all HER+ positive patients:

                     FCT       FC
MOS               13.8  v.  11.1 months  HR 0.74, P<0.0046
PFS                 6.7   v.   5.5 months  HR 0.71, P<0.0002

In addition, for the HER2+ patients, the subset analysis showed even better results:

                     FCT       FC
MOS               16.0  v.  11.8 months  HR 0.68

Adverse events were as expected for the relevant combinations tested and no new additional toxicities were seen.

These results are stunning and game changing – we can now expect the combination of 5FU/cisplatin plus trastuzumab to be the new standard of care for metastatic carcinoma of the stomach that overexpress HER-2.

What else was new in HER-2 positive cancers?  Well, there is a new compound in development from Wyeth called neratinib (HKI-272) which is ongoing in combination with trastuzumab in HER-2 positive breast cancer in patients who had previously progressed on Herceptin and a separate study investigating neratinib safety and efficacy when given with paclitaxel in patients with HER-2 dependent advanced solid tumors, suggesting that the compound is an active agent, although the data is still very prelimary at this stage.

None of the other abstracts in HER2 targeting therapies, including trastuzumab and lapatinib, stood out as much of the data was confirmation of previously reported data, but the gastric cancer data is well worth highlighting.  This cancer is more prevalent in Asian than Western populations and a number of factors may play a role in the aetiology of the disease including diet, smoking, etc.

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