What Makes a Treatment Clinically Meaningful?

August 2014 Vol 7, Special Issue ASCO 2014 Payers' Perspectives in Oncology

Two presentations at ASCO 2014 struck Jennifer Malin, MD, PhD, Medical Director of Oncology at WellPoint, Inc, as good examples of value in cancer care, but many other studies did not make the value-based list. Dr Malin described these studies at an ASCO Highlights of the Day session.

Proposed Criteria for Clinically Meaningful Outcomes
Dr Malin’s perspective was based on new criteria recently proposed by ASCO as a means of evaluating clinical trial results in terms of “clinically meaningful outcomes” (Ellis LM, et al. J Clin Oncol. 2014;32:1277-1280). De­pending on the tumor and previous treatment, any new regimen for metastatic disease should convey improvement in median overall survival (OS) of at least 2.5 months to 6 months.

“Powering studies to achieve these end points would be worth consideration. It would ensure that we make advances that provide clinically meaningful outcomes to patients, and it would also lead to smaller trial designs and would speed up innovation,” she predicted.

Studies Showing Value
Among studies presented at the meeting that clearly have clinical meaningfulness were 1 study of a subset of patients with lymphoma whose prognosis was poor and 1 study of patients with early-stage, HER2-positive breast cancer.

The phase 2 study of 64 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) showed that the addition of lenalidomide to R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone; R2CHOP) reduced the negative prognostic significance of the non–germinal center B-cell (GCB) phenotype (a subset of DLBCL). At 2 years, progression-free survival (PFS) for this subset of patients was 50%, and OS was 75% with the “R2CHOP” regimen, mirroring the outcomes in the patients with GCB.

This represented a 2-year relative increase of 30% in OS, at an estimated total drug cost of $73,682, and an incremental drug cost (for adding lenalidomide to R-CHOP) of $26,540.

“This regimen improves OS in patients previously known to have a poor prognosis. This is definitely a clinically meaningful improvement in outcome and provides great value, certainly in comparison to many other studies presented at ASCO,” Dr Malin commented.

A second study was a meta-analysis of 5 randomized trials of adjuvant trastuzumab. The analysis focused on 4220 HER2-positive patients with tumors ≤2 cm (mostly lymph node–positive), a group for whom the benefit of trastuzumab has not clearly been established.

Ciara C. O’Sullivan, MD, of the National Cancer Institute, Bethesda, MD, reported that trastuzumab reduced disease recurrences and deaths by approximately 30% in all groups, except for patients with 1 or no positive lymph nodes, whose mortality risk was reduced by only 2%.

“Trastuzumab clearly provides tremendous value for these patients, at a total drug cost of $81,336 and incremental cost of $76,601,” Dr Malin said. “It may have limited value, however, in the group with 0 to 1 positive nodes.”

Examples of Lack of Value
Dr Malin then described several studies that illustrated a lack of clinically meaningful outcomes, and therefore a lack of value. One was a phase 1 study of escalating doses of cabozantinib plus abiraterone in castration-­resistant prostate cancer in which a prostate-specific antigen decline of >75% was observed in 63% of men with the 20-mg dose and in 13% with the 40-mg dose. The investigators noted the combination’s tolerability and preliminary efficacy, which they claimed “support the investigation of this combination for further clinical development.”

According to Dr Malin, however, the findings indicated “limited to no improvement in outcomes,” and carried a total drug cost of $92,410 and an incremental drug cost of $32,521.

Another study evaluated the benefit of adding bevacizumab to trastuzumab plus docetaxel in the neoadjuvant breast cancer setting, finding a 20% relative increase in the rate of pathologic complete response. For this, the total drug cost was $103,976, and the incremental cost was $77,267.

The novel agent trebananib was evaluated in combination with paclitaxel and trastuzumab in patients with HER2-positive advanced breast cancer in a phase 1b study. Although the median PFS was approximately 18 months, which was deemed encouraging by the investigators, the estimated total drug and incremental drug costs—$325,530 and $170,000, respectively—gave Dr Malin pause.

“When our new drugs cost $170,000, we need to look for significant improvements in outcomes,” she commented.

Can Data Like These Guide Conversations?
Oncologists could use data such as these to have more meaningful conversations with patients about treatment options, Dr Malin suggested.

“There are often discussions with patients about what are meaningful outcomes, and these ‘value’ discussions often end up in debates as to whether a week, a month, a year is meaningful,” she said.

A pivotal study (Weeks JC, et al. N Engl J Med. 2012;367:1616-1625) revealed that 25% of patients with advanced lung cancer and approximately 35% of patients with metastatic breast cancer believed it was “very likely” their treatments could cure them.

“I posit that patients are looking for cures. If they understood the more marginal benefits that our treatments bring, they may be more likely to understand the tradeoffs in toxicity and cost, and be more likely not to want them,” she said.

Last modified: August 30, 2021
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