Category Archives: General Cynicism

Tasigna was recently (June 17,2010) approved for Philadelphia chromosome positive CML (Chronic Myelogenous Leukemia). You may be aware that CML is an unusual malignancy in that there is just one gene mutation with a number of minor variations–reciprocal translocation between chromosome 9 and 22 designated as t(9;22)(q34;q11). This tranlocation is occasionally found in acute lymphoblastic leukemia and acute myelogenous leukemia.

Having a single target appears to make the disease more susceptible to targeted drug intervention.

BCR-abl activates tyrosine kinase cell division controllers speeding up cell division and ultimately may cause blast crisis through the resulting genetic instability.

In the 90’s imatinib (Gleevec) was identified as active in CML blocking tyrosine kinase inhibitors. While not curative the drug resulted in immediate dramatic improvement in survival for CML patients. Some patients however in time became resistant and there are several newer tyrosine kinase inhibitors on the market that appear to work in these Gleevec resistant patients. Tasigna is one.

This is from the FDA:

The efficacy and safety of nilotinib in adults with newly diagnosed CP-CML was demonstrated in a single randomized, active-control, open-label multinational clinical trial. Eight hundred and forty-six patients were randomized to imatinib 400 mg QD (n = 283), nilotinib 300 mg BID (n = 282), or nilotinib 400 mg BID (n = 281). The primary objective was to compare the rate of major molecular response (MMR) at 12 months of nilotinib 300 mg BID and nilotinib 400 mg BID with that of imatinib 400 mg QD. MMR was defined as a ≤0.1% BCR-ABL/ABL % by international scale measured by RQ-PCR, which corresponds to a ≥3 log reduction of BCR-ABL transcript from standardized baseline. The rate of complete cytogenetic response (CCyR) by month 12 was the key secondary endpoint.

The primary efficacy endpoint, MMR at 12 months, was achieved in 63 patients [22% (95% CI: 18, 28)] in the imatinib arm, 125 patients [44% (95% CI: 38, 50)] in the nilotinib 300 mg BID arm, and 120 patients [43% (95% CI: 37, 49)]

In the nilotinib 400 mg BID arm. The differences were statistically significant

(p < 0.0001) for each nilotinib arm compared to the imatinib arm. CCyR rates by 12 months were 65% (95% CI: 59, 71) for the imatinib arm, 80% (95% CI: 75, 85) for the nilotinib 300 mg BID arm and 78% (95% CI: 73, 83) for the nilotinib 400 mg BID arm.

Medicynical Note: This is an example of a class of drugs, tyrosine kinase inhibitors, that are very effective but very expensive. To control CMS requires continued treatment often for many years at a cost approaching $100,000/year.

To return to a theme, this exceeds our average yearly and median incomes. Charging more for a single item that has become a necessity of life than the great majority of the population earns is unique to pharmaceuticals. Which in a way speaks volumes of our values?

It will be interesting to see if Tasigna is priced more reasonably. Consider that this drug was approved, as was Gleevec after a single clinical trial. And in the case of Gleevec much of the early research funding came from you and me through federal grants. I rather doubt we’ll see responsible pricing.

Drug pricing by any measure in our country is excessive and shows little signs of moderating. Our elected representatives appear to be handsomely rewarded for their support of the industry with large campaign contributions.

We need to look at patents and provide a market based means to reward companies that price drugs reasonably. We need to look at our insurance industry and their lax controls over drug expenditures. Providing cost efficacy studies on all these prohibitively expensive agents would help as well–but who will do them?

In review of the over 5000 abstracts presented at the recently concluded ASCO 2010 meeting, just 169 reports contained the word cost or costs.

Of these only 52 look at cost effectiveness. Most of these aimed at documenting cost rather than evaluating effectiveness.

Just 19 studies used the widely accepted QALY estimation to evaluate the cost effectiveness.

Of these 19 abstracts just three looked at the effectiveness of new targeted treatments, the most expensive medications ever marketed. These drugs cost more than the median and average income of U.S. citizens and one would have thought there would be interest in checking out the value of these advances.

The following are the three abstracts looking at cost-effectiveness:

Abstract # 6037 Cost-effectiveness of lapatinib plus capecitabine (LAP+C) versus capecitabine alone (C-only) or trastuzumab plus capecitabine (TZ+C) in women with HER2-positive metastatic breast cancer (MBC) who have received prior therapy with trastuzumab (TZ) from the U.K. National Health Service (NHS) perspective. British National Health Service

This study looked at time to progression and costs of the various regimens and then extrapolated from other studies survival data to provide cost effectiveness data. For the addition of lapatinib to capecitabine (the “standard treatment) the QALY was found to be 77,996 british pounds or about $109,000.

Abstract 3623 Cost-effectiveness analysis of the addition of bevacizumab to first-line chemotherapy in metastatic colorectal cancer. British Columbia Cancer Agency

Results: 943 patients were included: 611 from 2003/04 (pre-Bev era) and 332 from 2006 (Bev era). Median overall survival improved from 15.6 months in the pre-Bev era to 19.5 months in the Bev era (p=0.03). The weighted average cost of treatment per patient was $34,972 and $38,764 in the pre-Bev and Bev eras, respectively. In the Bev era, the cost of treatment resulted in an incremental cost-effectiveness ratio of $15,617/LYG, which translates into $62,468/QALY gained. Probabilistic sensitivity analyses produced an interquartile range of $38,900-$85,800/QALY, suggesting that the model is sensitive to the cost of systemic therapy. Conclusions: Even though Bev incurs in a high acquisition cost, it has also improved the cost-effectiveness of systemic therapy during the era in which it has been used.

link: Cost-effectiveness analysis of the addition of bevacizumab to first-line chemotherapy in metastatic colorectal cancer.

Abstract 1035: Indirect comparison of the cost-effectiveness of letrozole plus lapatinib (LET+LAP) versus anastrozole plus trastuzumab (ANA+TZ) as first-line treatment for postmenopausal women with HER2+ and HR+ metastatic breast cancer (MBC) from the U.K. National Health Service (NHS) perspective.

Shown in the Table (all results are discounted). LET+LAP yields more progression-free life years (PFLYs), life years (LYs), and QALYs than ANA+TZ. Medication costs are greater with LET+LAP, partly due to longer PFS. These higher costs are offset by savings in costs of drug administration. LAP+LET is therefore dominant (less costly and more QALYs) versus ANA+TZ. Conclusions: Letrozole plus lapatinib has greater effectiveness and lower cost from the U.K. NHS perspective when indirectly compared with anastrozole plus trastuzumab. Medicynical Note: The problem with this study is that the incremental benefit, cost effectivenenss, of trastuzumab in breast cancer is open to question “The addition of trastuzumab to capecitabine is estimated to cost on average an additional of €33 980 and to yield a gain of 0.35 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of €98 329/QALYs gained. Probabilistic sensitivity analysis showed that the willingness-to-pay threshold of €60 000/QALY was reached in 12% of cases.” You read that right a gain of .35 QALY’s for about $50,000. The question is whether any health care system can afford such expensive drugs.

Medicynical Note: Given that our health care system is number 1 in the world in inefficiency, one would have thought there would have been a number of studies from the U.S. evaluating cost efficacy. At this meeting there appears to have been no study of these high cost drugs from a U.S. institution. On second thought maybe there is a nexus here.

Unfortunately, in a “market” driven system with no checks on costs, no one is really interested in value. Our insurers, doctors and technology suppliers simply charge what they can/wish and pass the costs on to consumers, without regard for efficacy or cost. We need a brake in the system. It’s open to question whether the new health care law will provide it. What a non-system.