This year’s ASCO was packed with promising early stage trials, but very few positive late stage trials with an impact on medical practice. The two most important practice changing trials were phase III studies for Eli Lilly’s (LLY) Alimta and Roche’s (RHHBY.PK) Herceptin. These drugs are likely to enjoy a boost in revenues starting from next year, as both demonstrated impressive survival prolongation in lung and gastric cancer patients, respectively. The studies also underscore the paradigm shift in the industry towards personalized medicine, where a drug is given only to patients who have a high likelihood of deriving benefit. This article will focus on Alimta, which was, in my opinion the winner of ASCO 2009.
A new treatment line
Alimta was evaluated as maintenance therapy in Non small cell lung cancer (NSCLC), the largest oncology market. Maintenance therapy is a new treatment modality in which patients receive additional treatment straight after first line chemotherapy. Traditionally, patients receive first line treatment and are then re-treated with second line therapy only after the disease progresses or recurs. Some hope that slotting an additional treatment even before disease progression could benefit some, if not most patients. The concept of maintenance therapy for NSCLC has already been validated in previous trials, which created a lot of enthusiasm as well as controversy around this strategy.
Going into ASCO, a lot of attention was given to OSI’s (OSIP) and Roche’s Tarceva, which was evaluated in two studies as maintenance therapy for NSCLC. There was a great deal of enthusiasm towards Tarceva as maintenance therapy because it had two features which are considered ideal for this setting: It is an oral drug and it leads to relatively few side effects.
Although the Tarceva trials were technically successful, they turned out to be quite disappointing. Tarceva had a dramatic benefit in a subset of patients which comprises ~10% of the overall patient population, but showed a very modest gain in the general patient population. As a result, it seems that Tarceva, which is already approved for second line treatment will be used only for a minority of patients in the maintenance setting.
Luckily, Lilly’s Alimta more than compensated with an impressive data set in the same setting.
The Alimta study
The Alimta trial included 663 patients who were randomized to receive Alimta or placebo right after standard first line therapy. The trial was already presented at last year’s ASCO and showed encouraging results in terms of delaying disease progression. This year, investigators presented an update from the study, which included overall survival. Alimta increased survival by 2.8 months, which is fairly impressive given the typical survival of about a year for these patients.
However, Alimta seemed ineffective and even detrimental in a subset of patients with a specific tumor subtype called squamous NSCLC. A similar trend was also observed in previous trials with Alimta, and as a result, patients with squamous disease, who represent about a third of the NSCLC market, are not eligible for Alimta at any stage.
Supposedly, this should have a negative effect on Alimta, which instantly saw its addressable market shrink by ~30%. Other drugs for late stage NSCLC such as Tarceva and Taxotere are approved for all NSCLC patients. But the analysis also showed that in the remaining two thirds of patients, Alimta had an overwhelming benefit. The difference in activity between the two subsets mirrors data from two previously reported trials which led to the approval of Alimta in the first and second line settings. In both of these studies, Alimta proved superior to other chemo agents only in non-squamous patients.
In the recent maintenance study, non-squamous patients who received Alimta had a median survival of 15.5 months compared to 10.3 months for the placebo arm. A survival difference of over five months is unprecedented in NSCLC, far better than any other therapy has managed to achieve in this patient population. To put things in perspective, Avastin was approved based on a survival increase of 2 months to just over one year in a similar patient population.
