ESMO 2022 "Re-challenged" immunotherapy results after first-line treatment progress Presented at ESMO: First Phase III Study

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The European Society for Medical Oncology (ESMO) Annual Meeting is the most prestigious and influential oncology conference
in Europe.
The 2022 ESMO Conference will be held offline (Paris, France) and online from September 9 to 13, 2022, covering basic research, translational research and the latest clinical research progress, and will provide a broad and excellent academic platform
for clinical practice and multidisciplinary discussion.
A number of blockbuster studies in the field of lung cancer were presented at this year's ESMO Conference
.

In the oral presentation, Professor Mustafa Ozguroglu presented the results of EMPOWER-Lung 1 studies: 3-year follow-up results of first-line cemiplimab versus chemotherapy for PD-L1≥50% of patients, and the results of
first-line cemiplimab monotherapy followed by challenge immunotherapy + chemotherapy.
Details are as follows:

Professor Mustafa Ozguroglu

1 background

The EMPOWER-Lung 1 study showed that cemiplimab significantly improved overall survival (OS) with an acceptable safety
profile when treated with advanced NSCLC with first-line monotherapy compared with chemotherapy.
At this year's ESMO conference, researchers published the study's 3-year survival data
.
In addition, the investigators also published for the first time the results
of patients with disease progression (PD) who continued to use cemiplimab and added to a histological type-guided chemotherapy regimen.

2 methods

Enrolled patients were randomized in a 1:1 ratio to receive cemiplimab (350 mg, IV, every 3 weeks for 2 years) or the investigator's chosen chemotherapy regimen
.
Patients with PD (assessed by BIRC) are randomly assigned to receive cemiplimab, allowing patients to continue treatment with cemiplimab, adding up to 4 cycles of chemotherapy
.
To be included in the post-PD analysis, patients must receive at least one dose of chemotherapy and at least one imaging evaluation
after progression of cemiplimab therapy.
Response to cemiplimab+ chemotherapy was assessed by BIRC
.

Study design

3 Results

At a median follow-up of 37.
1 months, the median OS was 23.
4 months and 13.
7 months (HR=0.
634) in the cemiplimab group (N = 357) and chemotherapy (N = 355), respectively, and the median PFS in the two groups was 6.
3 months and 5.
3 months (HR = 0.
560),
respectively.

3-year OS and PFS outcomes in ITT populations

In 50% of patients with PD-L1≥, OS was 26.
1 months in the cemiplimab group and 13.
3 months in the chemotherapy group (HR=0.
57).

The median PFS in both groups was 8.
1 months and 5.
3 months
, respectively.

PD-L1 ≥ 3-year OS and PFS outcomes in 50% of the population

At 3-year follow-up, the objective response rate (ORR) was 42.
3% and 21.
4% in the cemiplimab group and chemotherapy group, respectively, with complete response (CR) rates of 8.
1% (29 cases) and 20.
% (7 cases) in the two groups, respectively, and the median duration of response (DOR) of 23.
6 months and 5.
9 months
, respectively.

Efficacy analysis

After disease progression, 64 patients continued to receive cemiplimab and added chemotherapy as second-line therapy, with an ORR of 31.
3%, a median OS of 15.
1 months, tolerable combination regimens, and serious intra-treatment adverse events (TEAEs)
occurred in 19 patients (29.
7%).

Analysis of the efficacy of second-line combination therapy

Combination therapy prolongs the patient's OS

4 Conclusion

Results at 3 years follow-up showed that cemiplimab improved PFS and OS compared with chemotherapy (compared with 1 year follow-up),
despite a crossover rate of 75%.
This study is the first phase III study
to challenge immunotherapy after advances in first-line PD-1 monotherapy.
The study reported that continued use of cemiplimab with chemotherapy (second-line therapy) continued to confer meaningful and durable ORR and OS benefits
after disease progression.
Combination regimens are superior to single-agent chemotherapy (after progression of first-line immune checkpoint inhibitor therapy) (historical data) as second-line therapy, with better
ORR and OS outcomes.
The results of the study support cemiplimab as a first-line no-chemotherapy option
for PD-L1≥50% of patients.

Reference:
LBA54-Three years survival outcome and continued cemiplimab (CEMI) beyond progression with the addition of chemotherapy (chemo) for patients (pts) with advanced nonsmall cell lung cancer （NSCLC）: The EMPOWER-Lung 1 trial.
2022 ESMO.