Targeted therapy in Lung Cancer: Which offers more value, Avastin, Erbitux or NEITHER!

Annotated abstract from the recent ASCO meetings.

This is a study comparing the cost of two very expensive, marginally effective treatments for lung cancer. The abstract purports to show that one of these drugs is less expensive and offers more “value” than the other. In fact neither is a “value” choice.

Title: A cost analysis (1) of treatment with bevacizumab plus cisplatin and gemcitabine (BCG) versus cetuximab plus vinorelbine and cisplatin (CVC) in patients with advanced or recurrent non-small cell lung cancer (NSCLC) in Germany

Authors: D. F. Heigener, C. Wiesner and R. Aultman

Affiliations: Krankenhaus Grosshansdorf, Grosshansdorf, Germany; Roche Pharma AG, Grenzach-Wyhlen, Germany; F. Hoffmann-La Roche, Basel, Switzerland

#: e17553

Background: Although new treatment options for advanced NSCLC can offer improved survival over standard treatment with chemotherapy (CT) they should also offer value for money.(2) Bevacizumab (BEV), a humanized monoclonal antibody (MAb) directed against vascular endothelial growth factor when combined with CT increases overall survival (median 13.6 months in the AVAiL study) and progression-free survival (PFS) in patients with advanced NSCLC when compared with CT alone.(3) Cetuximab (CTX), an IgG1 MAb which targets the epidermal growth factor receptor achieved a median survival time of 11.3 months when combined with CT in the FLEX study (4) and marketing authorization is anticipated in 2009. The aim of this study was to compare the costs of treating NSCLC with BCG or CVC in Germany. Methods: A Markov model was used to compare drug and administration costs associated with treating advanced or recurrent NSCLC with either BCG or CVC. The model assumes patients move from non-progressive to progressed disease prior to death, according to transition probabilities derived from an indirect comparison of the efficacy of BCG and CVC in terms of PFS using data from the respective pivotal trials and appropriate indirect comparison methodology. Cost data were derived from local sources. Drug cost assumed CT was given for up to 6 cycles, that CTX was administered at an initial dose of 400 mg/m2 followed by 250 mg/m2 weekly until progression and that BEV was administered at 7.5 mg/kg until progression. The model estimated average drug and administration costs per patient treated with either BCG or CVC. Results: The mean total costs of BCG treatment was Euro 4713 less per patient when compared with CVC (Euro 28342 vs. Euro 33055). The addition of BEV to CT was less costly than the addition of CTX to CT ( Euro 18796 vs. Euro 29502) and the administration costs were also lower (Euro 391 vs. Euro 1179). Conclusions: Targeted therapy using BEV is less costly than CTX in Germany and thus, from a budget perspective, offers the best value for money strategy for improving outcomes in patients with advanced NSCLC. Furthermore, costs savings with BCG in Germany are likely to be increased when gemcitabine comes off-patent in 2009.

Medicynical Annotations:

1. Cost Analysis: This abstract hardly describes a cost analysis. It is an attempt to encourage the use of bevacimimab (Avastin) instead of cetuximab (Erbitux). The study was sponsored by a drug company and the authors were company employees or recipients of financial support.

2. Value for money. It’s ironic to hear pharmaceutical company’s spokespeople tout value. In this case we are talking about two medications that are priced in the $10,000/month range. That’s more on an annual basis than the median and average incomes in the U.S. Yet these medication appear to have minimal positive effect in the setting described. That sure doesn’t sound like value!

3. Survival Benefit: The AVAIL trial found :

“At 12.5 months of follow-up, progression- free survival was significantly improved with bevacizumab, from 6.2 months in the placebo arm to 6.8 months with the 7.5 mg/kg dose (P = .0003) and to 6.6 months with the 15 mg/kg dose (P = .0456), Dr. Manegold reported.”

It also noted:

“No differences were observed in overall survival.”

Medicynical Note: The abstract doesn’t comment on the lack of a survival benefit. This omission is similar to the drug company’s press releases (google AVAIL study–press release here , and here .) But the various press releases do imply such a benefit when they claim: “Only first-line treatment to demonstrate extended survival in over a decade.” A claim that is marginal at best.

Dr. Manegold also furthers the fiction that there might be a survival benefit by stating that the 13 months survival was the “longest” for advanced NSCLC. However, he didn’t note that the survival in the group not receiving targeted therapy in his study was just as long

The only proven benefit from this expensive drug in the AVAIL study was a .6 month delay in disease progress.

(4) Compared with FLEX study: The other study referred to in the abstract is an ECOG (Easter Cooperative Oncology) group trial ( ECOG 4599 N Engl J Med 355:2542-2550, 2006). They compared carboplatin and taxotere with and without cetuximab (Erbitux). They found overall survival was 11.3 months in the cetuximab group and 10.1 months in the controls , an improvement of just 1.2 months. One-year survival was 47% in the cetuximab group and 42% in the control group.

Medicynical note: The AVAIL trial resulted in a .6 month delay in progression and no improvement in overall survival. The cetuximab trial shows slight benefit. These are hardly revolutionary improvements in patient care from drugs priced in the range of $100,000/year.

For what it’s worth the FLEX trials patients’ overall survival with cetuximab and chemotherapy was less than the control group (the group only receiving conventional chemotherapy) in the AVAIL trial.

The small delay in progression and improvement in survival (only found in the FLEX study) in these studies may be explained by patient selection, first study bias or simply be an indication of the limited efficacy of these agents in advanced lung cancer. Something that you would not know from the abstract or the PR releases.

Comparing the costs of very expensive agents with small benefits obfuscates whether they should actually be used in the first place.

It is a truism that drug companies market for profit rather than patient benefit.

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