Abstract 27P
Background
AR has been defined as radiological progression after initial response to ICI. CT may prevent primary resistance to ICI, halving the early mortality rate within the first 3 month of treatment. However, the impact of CT on AR upon ICI is currently unknown.
Methods
Randomized clinical trials (RCTs) testing ICI as single agent (SA-ICI) or in combination with CT (ICI+CT), CTLA-4 inhibitors (ICI-ICI) or both of them (ICI-ICI+CT) in metastatic NSCLC were searched in PubMed and EMBASE (until 05/2024). RCTs with available duration of response (DoR) data were eligible. Primary endpoint was to indirectly compare the AR rate between CT-containing with CT-free regimens. AR rate was computed using patients at risk at 6-months (mo) and 12-mo from DoR curves. Aggregate data were reported with risk ratio (RR) and pooled by random effect model. Time to event outcomes were retrieved from KM curves through the individual patient data (IPD)-from-KM method and compared by log rank test.
Results
16 RCTs (4297 patients) were included. AR rates at 6 and 12 mo were 15%–33% (SA-ICI), 26%–48% (ICI+CT), 19%–33% (ICI-ICI), 26%–46% (ICI-ICI-CT), respectively. A reduced risk of AR at 6 mo (RR: 0.56, 95% CI 0.50–0.63, p < 0.01, I2: 21%) and 12 mo (RR: 0.72, 95% CI 0.65–0.80, p < 0.01, I2: 53%) was observed with ICI+CT vs CT. Similarly, risk of AR at 6mo (RR: 0.51, 95% CI 0.37–0.69, p < 0.01, I2: 32%) and 12 mo (RR: 0.68, 95% CI 0.58–0.81, p < 0.01, I2: 0%) was lower with ICI-ICI+CT vs CT. Indirect comparison showed a higher risk of AR for ICI+CT vs SA-ICI (RR at 6 mo: 1.51, 95% CI 1.13–2.01; RR at 12 mo: 1.44, 95% CI 1.15–1.80) and for ICI-ICI-CT vs ICI-ICI (RR at 6 mo: 1.30, 95% CI 0.86–1.96; RR at 12 mo: 1.30, 95% CI 1.05–1.75). IPD analysis showed that median DoR was significantly worse both with ICI+PCT vs SA-ICI [11.5 mo (95% CI 10.7–12.4) vs 16.6 mo (95% CI 14.2–19), p=0.001] and with ICI-ICI+CT vs ICI-ICI [11.6 mo (95% CI 7–16.3) vs 18.9 mo (95% CI 14.7–23.2), p=0.001].
Conclusions
The addition of CT increases AR and reduces DoR upon ICI. A better selection of patients who may benefit from a first-line CTsparing ICI regimen would be crucial in order to reduce the risk of AR.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.