Yvonne Chao, MD, PhD, member, Cancer Biology Program, UPMC Hillman Cancer Center, assistant professor, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, discusses key trials leading to FDA approvals in metastatic non–small cell lung cancer (NSCLC).

The addition of a PD-1 or PD-L1 inhibitor to chemotherapy can improve overall survival (OS) in patients with metastatic NSCLC, based on data from the phase 3 KEYNOTE-189 (NCT02578680), KEYNOTE-407 (NCT02775435), and IMpower-150 (NCT02366143) trials, Chao begins.

KEYNOTE-189 evaluated the safety and efficacy of platinum-based chemotherapy with or without pembrolizumab (Keytruda) vs chemotherapy alone in patients with advanced or metastatic nonsquamous NSCLC who were not previously treated with systemic therapy for advanced disease. Data from this phase 3 trial led to 

the FDA approval of pembrolizumab used in combination with chemotherapy as a first-line treatment option for metastatic nonsquamous NSCLC

 in May 2017. Similarly, KEYNOTE-407 examined treatment carboplatin and paclitaxel or nab-paclitaxel (Abraxane) with or without pembrolizumab vs chemotherapy alone as a first-line treatment option in metastatic squamous NSCLC, leading to 

the FDA approval for pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel

 for the first-line treatment of metastatic squamous NSCLC in October 2018.

Finally, the randomized, open-label IMpower-150 study evaluated the safety and efficacy of atezolizumab (Tecentriq) in combination with carboplatin plus paclitaxel with or without bevacizumab (Avastin), compared with treatment of carboplatin plus paclitaxel and bevacizumab in chemotherapy-naïve participants with stage IV nonsquamous NSCLC.

™, Chao also highlighted information from trials published within the last few years that led to FDA approvals for nivolumab (Opdivo), an PD-1 inhibitor, in combination with ipilimumab (Yervoy), an CTLA-4 inhibitor, either with or without chemotherapy, for the frontline treatment of NSCLC. Data from the phase 3 CheckMate 227 trial (NCT02477826) led to the approval of the combination of nivolumab plus ipilimumab, and findings from the phase 3 CheckMate 9LA trial (NCT03215706) supported the approval of nivolumab and ipilimumab plus chemotherapy. Results of these trials showed that combination immunotherapy regimens with or without chemotherapy can lead to improved OS and durable responses compared with chemotherapy alone, Chao concludes.

Videos

Yvonne Chao, MD, PhD, discusses key trials leading to FDA approvals in metastatic non–small cell lung cancer.

Dr. Chao on Key Trials Leading to FDA Approvals in Metastatic NSCLC

Yvonne Chao, MD, PhD, member, Cancer Biology Program, UPMC Hillman Cancer Center, assistant professor, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, discusses the study of various PD-L1 inhibitors in patients with non–small cell lung cancer (NSCLC).

Findings from the phase 3 Study 16113/EMPOWER-Lung 3 trial (NCT03409614) led to the 

FDA approval of the anti–PD-1 inhibitor cemiplimab-rwlc (Libtayo) in combination with platinum-based chemotherapy

 for the treatment of adult patients with advanced NSCLC with no 

 aberrations in November 2022. The phase 3 trial enrolled 466 patients with locally advanced NSCLC who were not eligible for surgical resection, who were not eligible for definitive chemoradiation, and patients with metastatic disease who had not received prior systemic treatment. The addition of cemiplimab led to a statistically significant improvement in overall survival (OS) vs chemotherapy alone.

Previously, in February 2021, the FDA approved cemiplimab monotherapy as a frontline treatment for patients with advanced NSCLC with a PD-L1 expression level of 50% or higher. That approval was based on data from the phase 3 EMPOWER-Lung 1 trial (NCT033088540), which also demonstrated an improvement in OS vs chemotherapy.

Another key trial evaluating PD-L1 inhibitors in NSCLC was the phase 3 CheckMate 227 trial (NCT02477826), which evaluated nivolumab (Opdivo) in combination with ipilimumab (Yervoy) vs platinum doublet chemotherapy alone in patients with treatment-naïve NSCLC. Data from the study demonstrated improved OS compared with chemotherapy alone, Chao notes.

The phase 3 CheckMate 9LA (NCT03215706) trial expanded on CheckMate 22y by evaluating 2 cycles of chemotherapy in combination with nivolumab plus ipilimumab compared with chemotherapy alon in previously untreated patients with NSCLC, Chao says. This study also showed that the immunotherapy-based combination also led to improvements in OS and progression-free survival, Chao concludes.

Yvonne Chao, MD, PhD, discusses the study of various PD-L1 inhibitors in patients with non–small cell lung cancer.

Yvonne Chao, MD, PhD

Articles

Dr. Chao on Key Trials Leading to FDA Approvals in Metastatic NSCLC

Dr. Chao on the Study of PD-L1 Inhibitors with NSCLC