Notable Lung Cancer Immunotherapy Research Led by Turkish Oncologists

Lung cancer remains the leading cause of cancer death worldwide, and non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer cases.

EMPOWER-Lung 1 evaluates cemiplimab in advanced NSCLC with PD-L1 tumour expression of 50% or more. Cemiplimab is an anti-PD-1 immunotherapy assessed as single-agent treatment. The study matters for expanding treatment options and improving long-term outcomes.

This international phase-3 clinical trial was led by successful Turkish medical oncologists Professor Mustafa Özgüroğlu and Professor Saadettin Kılıçkap. The research was published on 14 August 2023 in The LANCET Oncology. It involved 138 cancer centres in 24 countries and included distinguished Turkish medical oncologists such as Professors Ahmet Sezer, Mahmut Gümüş and İrfan Çiçin as authors.

Lasting Survival Benefit with First-Line Cemiplimab

In EMPOWER-Lung 1, after median follow-up of approximately 3 years, patients receiving first-line systemic cemiplimab had better progression-free survival (PFS) and overall survival than those receiving first-line chemotherapy.

The trial included previously untreated advanced non-small cell lung cancer (NSCLC). A total of 712 patients were randomised to cemiplimab (357 patients) or investigator-chosen chemotherapy (355 patients).

Baseline characteristics were balanced between arms. Median follow-up was 37.1 months in both.

Of the 712 enrolled patients, 565 had tumour PD-L1 expression of 50% or higher.

Results

• Median overall survival was 23.4 months with cemiplimab versus 13.7 months with chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval 0.52–0.77; P <0.0001).
• Median PFS was 6.3 versus 5.3 months, respectively (HR 0.56; 95% CI 0.47–0.67; P <0.0001).
• Objective response rates were 42% with cemiplimab and 21% with chemotherapy. Median response durations were 23.6 and 5.9 months, respectively.
• Treatment-related adverse effects occurred in 63% of the cemiplimab arm and 90% of the chemotherapy arm. Grade 3 or higher treatment-related adverse effects occurred in 18% and 40%, respectively.

PD-L1 Subgroup Results

Among the 565 patients with tumour PD-L1 expression of 50% or higher, 284 were assigned to cemiplimab and 281 to chemotherapy.

• Median follow-up in this subgroup was 34.9 months with cemiplimab and 35.0 months with chemotherapy.
• Median overall survival was 26.1 months with cemiplimab versus 13.3 months with chemotherapy (HR 0.57; 95% CI 0.46–0.71; P <0.0001).
• Median PFS was 8.1 versus 5.3 months, respectively (HR 0.51; 95% CI 0.42–0.62; P <0.0001).
• Objective response rates were 46% with cemiplimab and 21% with chemotherapy. This suggests that cemiplimab caused tumour shrinkage in more than half of patients.

Second-Line Treatment

Of 106 patients who received second-line treatments after progression, 64 received cemiplimab plus chemotherapy at documented progression.

In the group receiving second-line cemiplimab plus chemotherapy,

• the objective response rate was 31%,
• median PFS was 6.6 months, and
• the median overall response rate was 27.4 months.

The researchers concluded that adding chemotherapy to cemiplimab at progression could provide a new second-line treatment. They also confirmed that cemiplimab’s survival benefit as monotherapy supports its use as first-line treatment in this group.

What Is This Study’s Most Important Contribution to Oncology Practice?

A New Second-Line Treatment Option: Adding chemotherapy to cemiplimab at progression could provide a new second-line treatment, increasing the options available when disease progresses.

This conclusion was drawn from the whole patient group. Available information does not specify a particular relationship between PD-L1 levels and the effectiveness of second-line treatment.