Keynote 189
What is/are the primary endpoints of KN 189?
OS and PFS by independent central review
What are the CT backbone options for KN 407?
Carboplatin plus paclitaxel or nab-paclitaxel
What is the effective cross-over rate reported at the 5-Year FU?
66%
Name 2 differences of IM110 vs KN024 in study design
1. 35 cycles in KN024 vs treatment until PD in IM110
2. crossover in KN024 vs no crossover in IM110
3. second course allowed in KN024 vs no second course in IM110
4. 22C3 in KN024 vs SP142 in IM110
5. PFS in KN024 vs OS WT in IM110 for primary endpoint
6. pac/carbo allowed for SQ in KN024 vs no pac/carbo in IM110
How many cycles of CT are offered in CM9LA in the induction phase?
2 cycles
What are the mOS and HR of KEYTRUDA-CT vs CT at the 4-Year FU?
22m vs 10.6m (HR: 0.60; 95% CI 0.50-0.72)
What are the mOS and HR of KEYTRUDA-CT vs CT at the 3-Year FU?
17.2m vs 11.6m (HR: 0.71; 95% CI 0.59-0.86)
What are the mOS and HR of KEYTRUDA vs CT at the 5-Year FU?
26.3m vs 13.4m (HR: 0.62; 95% CI 0.48-0.81)
What are the exploratory mOS and HR in IM110 (atezolizumab vs CT) in the updated analysis?
20.2m vs 14.7m (HR 0.76; 95% CI 0.54-1.09)
Treatment regimen studied in CM 9LA
Nivo 360mg Q3W + Ipi 1mg.kg Q6W + 2 cycles of platinum doublet chemo Q3W vs Chemo Q3W for 4 cycles
What are the mOS and HR of KEYTRUDA-CT vs CT at the 4-Year FU for TPS<1%?
TPS <1% - 17.2m vs 10.2m (HR: 0.52)
What is the PFS2 and HR of KEYTRUDA-CT vs CT at the 3-Year FU?
13.8m vs 9.1m (HR: 0.59)
What is the landmark OS rate of KEYTRUDA vs CT at 5-Year?
31.9% vs 16.3%
What are the updated mOS of ABCP vs BCP in the IM150 final analysis for ITT population?
19.8m vs 15.0m (HR: 0.80; 95% CI 0.68-0.95)
What are the mOS and HR in CM9LA (nivolumab-ipilimumab-CT) at the 2-Year update?
15.8m vs 11.0m (HR: 0.72; 95% CI 0.61-0.86)
Which patients should I use KEYTRUDA as first-line -monotherapy vs combination therapy?
KEYTRUDA in combination with chemotherapy should be considered as the first-line treatment for all appropriate patients with metastatic NSCLC, including patients with no PD-L1 expression or are untested.
What is the latest NCCN recommendation of KEYTRUDA-CT regardless of histology?
Category 1 Preferred
For my NSCLC patients with TPS >50%, should I use KEYTRUDA monotherapy or KEYTRUDA-CT combination?
Depending on the patient profile, preference and treatment objectives. Patients who wish to achieve a greater tumor control should be offered KEYTRUDA-CT combination while PD-L1 expressing patients who are inappropriate for KEYTRUDA-CT would be suitable for KEYTRUDA monotherapy.
The results of IM110 for the high or intermediate (TC2/3 or IC2/3) looks to be comparable vs KN024.
Statistically significant OS improvement was not observed in the high or intermediate (TC2/3 or IC2/3) PD-L1 expression patients with mOS of 19.9m vs 16.1m (HR: 0.87; 95% CI 0.66-1.14).
In contrast, KN024 has demonstrated consistent, durable OS benefit with close to doubling of OS landmark at 5-Year.
CM9LA offers limited course of CT and is more friendly to patients who refuse or sceptical to CT.
There is no clinical evidence showing the benefit of 2 cycles CT prior to the read-out of CM9LA hence the design rationale is questionable.
In contrast, KN189 and KN407 are designed upon evidence and clinical practice of clinicians.
Why is testing still recommended when KEYTRUDA combination therapy can be used regardless of PD-L1 expression? Do I still need to test my NSCLC patients for PD-L1 expression?
We recommend that you test your NSCLC patients at diagnosis because knowing a patient’s PD-L1 expression allows you to personalize your treatment. In addition, it allows you an informed discussion with your patients and use the PD-L1 result to guide treatment decision.
Looking at the OS and PFS curve in patients with TPS <1% I am not convinced to use KEYTRUDA-CT in this subgroup of patients
KEYTRUDA-CT continues to show a favorable OS trend for patients with TPS<1% despite longer-term FU with an absolute median OS benefit of 4m.
I believe Atezolizumab and KEYTRUDA are equally good for NSCLC patients with high PD-L1 expression. I will use whichever that is cheaper.
Cross-trial comparisons are difficult to interpret. IM110 met the OS end point for EGFR/ALK–negative patients with PD-L1 expression of TC3 or IC3. This is estimated to accounts for ~15% of the NSCLC wild-type population as determined by the
SP142 PD-L1 assay. SP142 (TC3/ IC3) has been documented in Blueprint study to have a discordance vs other established PD-L1 assays thus potential risk of biases.
KEYTRUDA has demonstrated consistent, durable OS benefit, in combination or as monotherapy, over CT in 5 phase 3 studies in patients with advanced NSCLC.
KEYTRUDA demonstrated durable benefits. In the updated 5-Year FU of KN024, median OS nearly doubled: 26.3 months (95% CI 18.3–40.4) with KEYTRUDA vs 13.4 months (95% CI, 9.4–18.3) with CT.
I prefer to use IM150 regimen for my patients with liver metastases as the addition of bevacizumab leads to higher ORR and tumor control.
Cross-trial comparisons are difficult to interpret especially in the subgroups setting that are not powered enough. In the final analysis of IM150, the ABCP vs BCP mOS for ITT with liver metastases are 13.2m vs 9.1m (HR: 0.67) but has crossed the upper boundaries of 95% CI.
In KN189, the mOS for liver metastases patients are 12.6m vs 6.6m with KEYTRUDA-CT and CT respectively (HR: 0.62; 95% CI 0.39-0.98). While the ORR might seem higher in the initial phase of treatment with IM150, KN189 has shown to have more durable tumor responses after 1-Year in a MAIC.
Nivolumab-ipilimumab-CT seems like a more efficacious regimen for patients whose tumors do not express PD-L1.
In KN189 and the pooled analysis of KN189/KN407/KN021G, KEYTRUDA-CT has consistently demonstrated favorable OS trend for WT patients with NSQ and SQ histology.