WCLC 2022 Exploration of first-line immune combination therapy for ES-SCLC, 3-year follow-up results of KEYNOTE-604 study released!

The 2022 International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer (WCLC) will be held in offline + online format from August 6 to 9, 2022

Phase III study KEYNOTE-604 suggested that pembrolizumab combined with EP as first-line treatment of ES-SCLC patients could significantly improve PFS compared with placebo combined with EP (HR=0.

The study included previously untreated patients with ES-SCLC who were randomly assigned 1:1 to receive pembrolizumab 200 mg Q3W or placebo in combination with 4 cycles of standard-dose EP regimen, pembrolizumab Treatment with mAb or placebo lasted up to 35 cycles

Figure 1 Study Design

As of September 21, 2021, a total of 453 patients (pembrolizumab+EP, n=228; placebo+EP, n=225) were included in the ITT population of the study

Table 1 Baseline status of patients

OS analysis showed that pembrolizumab + EP improved the survival benefit of patients, with median OS of 10.

Figure 2 OS and subgroup analysis of patients

PFS analysis showed a median PFS of 4.
8 months (95%CI: 4.
3-5.
4) in the pembrolizumab+EP group and 4.
3 months (95%CI: 4.
2-) in the placebo+EP group 4.
5), the 3-year PFS rates of the two groups were 6.
9% and 0.
5%, respectively.
The specific PFS and subgroup analysis are shown in Figure 3
.

Figure 3 PFS and subgroup analysis of patients

Analysis of patients' disease remission showed that the ORR of the pembrolizumab + EP group was 70.
6%, and the median DOR was 4.
2 months; the ORR of the placebo + EP group was 61.
8%, and the median DOR was 3.
7 months, As shown in Table 2
.

Table 2 Disease remission of patients

In the safety analysis, grade 3-5 adverse events of any cause occurred in 78.
9% and 77.
1% of patients in the pembrolizumab+EP group and placebo+EP group, respectively
.

The incidence of immune-related adverse events in the two groups was 27.
4% and 12.
1%, respectively, and the incidence of grade 3-5 immune-related adverse events was 8.
1% and 1.
3%, respectively
.

As shown in Figure 4, a total of 18 patients completed 35 cycles of pembrolizumab.
The ORR of these 18 patients was 100% (95% CI: 81.
5%-100%), and the median DOR was not reached, The median OS was not reached, and the 2-year OS rate was 72.
2% (95% CI: 39.
5%-89.
2%) in patients starting from completing 35 cycles of pembrolizumab treatment (approximately 2 years)
.

Figure 4 Benefit analysis of patients who completed 35 cycles of treatment

For previously untreated ES-SCLC patients, pembrolizumab + EP still showed a superior survival benefit and a manageable safety profile at long-term follow-up compared with placebo + EP
.

The 3-year OS rate of patients in the pembrolizumab + EP group can reach 15.
5%, compared with 5.
9% in the control group, and patients who complete the entire treatment cycle can achieve better survival benefits
.

Based on the above data, the researchers believe that the application of pembrolizumab combination strategy in ES-SCLC patients should continue to be explored
.

references

1.
OA12.
06 - First-Line Pembrolizumab or Placebo Combined With Etoposide and Platinum for ES-SCLC: KEYNOTE-604 Long-Term Follow-Up Results.

Edit: Youshi

Reviewer: Jiang Zhou

Typography: Youshi

Execution: Traveller