Absolute Benefit in ROS1-Positive Metastatic NSCLC
Absolute benefit refers to the actual percentage point improvement in survival or response rates between treatment and control groups, expressed as the arithmetic difference rather than a relative ratio. 1
Definition and Clinical Context
Absolute benefit quantifies treatment efficacy by calculating the direct difference in outcomes between intervention and comparison groups. In the context of ROS1-positive metastatic NSCLC, this metric provides the most clinically meaningful assessment of treatment value. 1
Key Characteristics
- Absolute benefit is expressed as a percentage point difference, such as "5% improvement in 5-year survival" (e.g., from 50% to 55%), rather than relative terms like "10% relative risk reduction" 1
- This measure directly translates to the number of patients who benefit from a given intervention, making it more interpretable for clinical decision-making than relative measures 1
- In early-stage NSCLC, adjuvant cisplatin-based chemotherapy demonstrated an absolute survival benefit of 4% at 5 years in meta-analysis, though this was not statistically significant at the time 1
Application to ROS1-Positive NSCLC Treatment
For ROS1-positive metastatic NSCLC specifically, absolute benefit manifests in several measurable outcomes:
Objective Response Rate (ORR)
- Repotrectinib achieved a 79% ORR in treatment-naïve ROS1-positive patients compared to historical chemotherapy controls (approximately 30-40%), representing an absolute benefit of approximately 40 percentage points 1
- Crizotinib demonstrated a 70.7% ORR versus 53.3% for pemetrexed-based chemotherapy, yielding an absolute benefit of approximately 17 percentage points 2
Progression-Free Survival (PFS)
- Repotrectinib produced a median PFS of 35.7 months in treatment-naïve patients versus historical chemotherapy controls of 5-8 months, representing an absolute improvement of approximately 28-30 months 1
- The estimated 2-year PFS for ROS1-positive patients on crizotinib was 54% compared to significantly lower rates with chemotherapy alone 3
Clinical Interpretation Pitfalls
Avoid confusing absolute benefit with relative risk reduction, which can overstate treatment effects. For example, a reduction in mortality from 2% to 1% represents a 50% relative risk reduction but only a 1% absolute benefit—meaning 100 patients must be treated to prevent one death. 1
In ROS1-positive NSCLC, the absolute benefits of targeted therapy are substantial because baseline response rates to chemotherapy are modest (30-50%), while TKI response rates exceed 70%, creating large absolute differences that translate to meaningful clinical improvements. 1, 3, 2
Brain metastases represent a critical consideration: While TKIs demonstrate superior systemic control, brain metastases developed more frequently during TKI treatment (15.5%) than during pemetrexed-based chemotherapy (6.7%), though this likely reflects longer survival allowing time for CNS progression rather than treatment failure. 2