Cutting-edge cancer treatments showcased at ESMO
pharmafile | October 18, 2010 | Feature | Research and Development | AstraZeneca, Boehringer, Cancer, Cancer Conference, Johnson & Johnson, Novartis, personalised medicine
The search for a ‘silver bullet’ against cancer has failed, for now, with the battle against the disease turning instead to increasingly personalised treatments.
Pharma is focusing on the genetic sub types of the disease, building up an arsenal of weapons against what is now seen as a plurality of diseases, and the latest information on many of these were presented at the recent ESMO meeting.
The 35th annual European Society of Medical Oncology congress included updates from Roche on its targeted antibody TDM-1, AstraZeneca on Iressa and J&J on its new prostate cancer drug abiraterone acetate.
Roche
Cancer specialist Roche has had a difficult year with its multi-indicated cancer drug Avastin losing its US breast cancer indication and still prevented from routine NHS use by UK drugs watchdog NICE.
So the ESMO congress provided something of a reprieve from recent troubles, with new, old and updated cancer drugs taking the spotlight at Milan.
The first is its T-DM1 candidate, made in conjunction with US biotech firm ImmunoGen, that builds upon the HER2+ targeting capabilities of its established breast cancer drug Herceptin.
TDM-1 uses a new, targeted antibody that can kill breast cancer cells at a later stage of the disease after the failure of other chemotherapy and cancer drugs.
Presenting the phase II data, Professor Perez said: “This is the first ever presentation of an anti-HER2 antibody-drug conjugate used as first-line therapy for patients with advanced breast cancer.
“We are encouraged by the results. The study demonstrated that TDM-1 has very good anti-tumour activity as well as much lower toxicity when evaluated side-by-side to the older ‘standard’.”
These data may be positive, but Roche received a major setback in August when the FDA sent it a ‘refuse to file’ letter for TDM-1.
Roche has said it will re-submit in mid-2012, but may need to do more to convince the US regulator that this particular mechanism of action is safe for patients.
The company’s Tarceva also performed well in a subgroup of non-small cell lung cancer patients (NSCLC). Researchers reported patients whose tumour presented the epidermal growth factor receptor (EGFR), had triple the progression-free survival rates after taking Tarceva, compared to those on standard chemotherapy.
Roche has submitted Tarceva, which made over $1 billion last year, as a first line treatment for EGFR-positive patients in Europe.
Finally, the company also had preliminary results from a phase II study of its unique monovalent antibody MetMAb in combination with Tarceva. This showed that patients with high MET-expressing NSCLC taking Tarceva went for nearly twice as long without their disease getting worse, compared to those given placebo.
Richard Scheller, head of Genentech research and early development, said: “Lung cancer remains an area of high unmet medical need, and our new data with MetMAb is an example of how a targeted, personalised approach may help improve outcomes in this hard-to-treat disease.”
AstraZeneca
There was new phase II data from AstraZeneca at ESMO for its non-small cell lung cancer drug Iressa.
Data from the IPASS study showed that there was no significant difference between Iressa and carboplatin/paclitaxel (a ‘doublet’ chemotherapy) in the overall population.
There was also no significant difference between treatment arms for overall survival in the subgroups defined by EGFR mutation status.
The IPASS data confirmed that patients with EGFR mutation-positive advanced NSCLC had better outcomes, regardless of which treatment arm they were in, compared to patients with EGFR mutation-negative disease.
Median survival times were around 22 months for EGFR mutation-positive patients, but only 11-12 months for EGFR mutation-negative patients, indicating the drug’s efficacy in the targeted population.
Professor Alison Armour, medical science director for AstraZeneca and IPASS investigator, said: “IPASS data reinforce that there should be a move towards recognising that lung cancer is a complex disease with distinct subtypes requiring targeted medicines.”
Johnson & Johnson
Johnson & Johnson saw the most excitement in Milan over its new prostate cancer drug abiraterone acetate.
Results from a pre-specified interim analysis of a randomised, placebo-controlled phase III study, COU-AA-301, demonstrated that patients treated with abiraterone acetate, plus low-dose prednisone/prednisolone, showed a significant improvement in overall survival compared to patients treated with prednisone/prednisolone plus placebo.
The trial showed that those given the drug, together with a low-dose steroid lived, on average, 14.8 months while those on steroids plus a placebo survived 10.9 months.
“That 3.9 months may not seem much but you have to understand that in the history of prostate cancer only four drugs have previously ever shown a survival benefit,” said lead investigator Johann de Bono of Britain’s Institute of Cancer Research.
It was also significant as it was one of the few late-stage trials in Milan to show an increase of overall survival, an endpoint that many pharma companies do not use as most drugs struggle to meet it.
J&J plans to file marketing applications for abiraterone acetate with regulatory authorities in the US and Europe by the end of the year.
Novartis
There was disappointing news from Novartis, whose Afinitor, in combination with its Sandostatin LAR, failed to meet its primary endpoint of improving progression free survival, in a phase III study to reduce tumour growth in patients with advanced neuroendocrine tumours.
The company said that on average, patients treated with Afinitor and Sandostatin LAR lived for 16.4 months before their tumours progressed again, compared to 11.3 months for patients treated with Sandostatin LAR and placebo, but Novartis said this was not statistically significant.
Boehringer Ingelheim
Boehringer Ingelheim released the latest results of its novel NSCLC drug candidate Tovok (afatinib), which it aims to position as the first available second-line treatment for NSCLC patients.
Results from the LUX-Lung1 phase II trial suggest that Tovok is active in late-stage patients with NSCLC, while in the LUX-Lung 2 phase II trial, Tovok demonstrated encouraging activity in advanced NSCLC patients that have a mutated EGFR.
Even though the LUX-Lung 1 trial did not meet the primary endpoint of prolonging overall survival, Tovok did lead to a three-fold extension of progression-free survival, the secondary endpoint, from 1.1 months to 3.3 months over placebo.
It is being developed to counter-act the resistance to established drugs such as AstraZeneca’s Iressa and Roche’s Tarceva.
A targeted future for cancer drugs
This year’s congress showcased a number of significant advances in treating cancer and highlighted the way pharma research will narrow its focus to help more and more patients over the next 10 years.
But the trend towards increasing personalisation means many drugs are so targeted that they are effective in only small proportions of the population.
Iressa, for example, is only effective in around 15% of NSCLC patients and Pfizer’s lung cancer candidate crizotinib, presented at US congress ASCO earlier this year, can only help between 1 and 5% of the population.
So the future is likely to rely on the kind of progress made by the Human Genome Project in unveiling new genes and thus helping to pinpoint new mutations that cause cancer so more treatments can be made to be more targeted.
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