Abstract P5-15-02: The benefit of targeted therapeutics in medical oncology since the development of trastuzumab
Bibliographic record
Abstract
Abstract Background: Trastuzumab has achieved widespread approval and funding across much of the developed world for metastatic and, later, adjuvant HER2/neu positive breast cancer. This success may be attributed to a favorable therapeutic index and incremental cost-effectiveness ratio (ICER). Has the success of trastuzumab been replicated by newer therapeutics? Methods: The societal marginal benefit gained from a new drug can be estimated by calculating the difference between the incremental quality-adjusted life-years gained (QALY) and the maximum willingness-to-pay (WTP) for the increase in health by society. A systematic review was employed to amass all English-language cost-effectiveness analyses (CEA) on small-molecule inhibitors and monoclonal antibodies approved for the treatment of solid malignancies. Searches of PubMed and EMBASE provided citations published between 1995 and February 5, 2012. Two reviewers each independently assessed the eligibility of all abstracts and subsequently abstracted data from published abstracts and manuscripts. CEAs comparing two experimental treatments to each other were excluded. Incremental costs and ICERs were converted from their native currency to U.S. dollars according to their average exchange-rates since publication. Results: Of the 1,576 citations identified, 60 were included in the final analysis. Tumor-types studied included breast, colorectal, gastric, gastrointestinal stromal, head and neck, non-small cell lung, ovarian, hepatocellular, and renal cancers, and pancreatic neuro-endocrine tumor. Studies originated from USA (14%), continental Europe (37%), England (12%), Canada (12%), Asia (11%), and Latin America (12%). Median WTP was $65,000 (range $30,000-$297,000). 92% of all CEAs included considered to be cost-effective by the CEA's authors. Trastuzumab was studied for breast cancer treatment by 13 CEAs in the adjuvant setting and by 3 CEAs in the metastatic setting. Trastuzumab is significantly more cost-effective than other targeted treatments (mean ICER $32,000 vs. $108,000, p = 0.001). 84% of trastuzumab studies found its ICER<$40,000, but only 32% of other CEAs met this threshold. Trastuzumab may be more cost-effective if employed in the adjuvant setting compared to the metastatic setting (mean ICER $18,000 vs. $29,000, p = 0.12). After trastuzumab, the most favorable treatments by ICER were imatinib for GIST, cetuximab with radiation for head and neck cancer, and sorafenib for hepatocellular carcinoma. There was no apparent relationship between the country of origin in which the CEA was conducted and the ICER estimate. Conclusion: Trastuzumab represents a significant achievement in clinical medicine and also provides greater value than newer targeted chemotherapy, in general. Newer therapeutics are being priced close to the maximum WTP of society. Adjuvant therapy may prove more cost-effective than therapy in the metastatic setting. Unless better pricing arrangements can be made or future therapies produce greater incremental clinical benefits for the same cost, it seems unlikely that the societal success of trastuzumab will be replicated. However, this analysis assumes that maximizing societal health, not profit, is of primary concern. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-15-02.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.012 | 0.059 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.004 |
| Bibliometrics | 0.016 | 0.021 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.016 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".