This seems like a straightforward question, but clearly depends on what you mean by “best”. Some drugs will be more efficacious and have more adverse events; other drugs may be less efficacious but have fewer adverse events. What if a one drug shows an 80% improvement in progression free survival (PFS), but a 50% improvement in overall survival (OS); whereas another drug shows only a 50% increase in progression free survival but an 80% increase in overall survival. Patient preferences over these treatment outcomes can vary.
But even if we just consider gains in OS, how should this be measured? Average survival? Median survival? Share of patients that survive X years? Number needed to treat (NNT)? Does this matter?
In fact, a recent article by Karweit et al (2017) found that it does. The authors looked at the following ways of measuring improvements in overall survival:
- Median OS
- mean OS
- 1-year survival rate
- NNT to avoid 1 death at 1 year
The authors compare these outcomes across treatments for breast cancer (BC), colorectal cancer (CRC), melanoma, non–small cell lung cancer (NSCLC), prostate cancer (PC), and renal cell cancer (RCC).
So which drug was best? It depends on the outcome you use.
- Breast cancer: ado-trastuzumab emtansine demonstrated the greatest improvement in median OS, pertuzumab in mean OS, eribulin mesylate in 1-year survival rate; trastuzumab demonstrated the lowest NNT. For CRC, bevacizumab demonstrated the greatest improvements in median OS and 1-year survival rate, as well as the lowest NNT, whereas cetuximab had the greatest improvement in mean OS.
- Colorectal cancer: Capecitabine, the only agent assessed in CRC with a nonplacebo comparator, showed the least improvement across all 3 outcomes. For melanoma, ipilimumab showed the greatest benefit with all 3 outcomes.
- NSCLC: Pemetrexed exhibited the greatest improvements of median and mean OS, whereas erlotinib showed the greatest improvement in 1-year survival rate and the lowest NNT.
- Prostate cancer: Enzalutamide demonstrated the greatest improvement in median OS, sipuleucel-T showed the greatest improvement in mean OS, and abiraterone had the greatest improvement in 1-year survival rate and the lowest NNT.
- RCC: Sunitinib demonstrated the greatest improvements in both median and mean OS, whereas temsirolimus had the greatest improvement in 1-year survival rate and the lowest NNT.
The authors propose a measure portfolio to more comprehsnively measure efficacy. They conclude as follows:
Our preliminary qualitative and quantitative analysis, which used more and different metrics than may be the standard, suggests that a broad array of survival outcomes are required to fully assess and benchmark the relative clinical value of anticancer agents. This approach becomes progressively more important as drugs transition from clinical development to regulatory approval and widespread application. The portfolio of measures assessing impact needs to be more broadly meaningful in general populations; our concept of a measure portfolio starts to move in that direction.
- Jennifer Karweit, MS; Srividya Kotapati, PharmD; Samuel Wagner, PhD; James W. Shaw, PhD, PharmD, MPH; Steffan W. Wolfe, BA; and Amy P. Abernethy, MD, PhD. Jennifer Karweit, MS; Srividya Kotapati, PharmD; Samuel Wagner, PhD; James W. Shaw, PhD, PharmD, MPH; Steffan W. Wolfe, BA; and Amy P. Abernethy, MD, PhD. An Expanded Portfolio of Survival Metrics for Assessing Anticancer Agents. JMCP. January 17, 2017