Leora Horn, MD, MSc, Ingram Associate Professor of Cancer Research; associate professor of medicine (Hematology and Oncology); assistant director of the Educator Development Program and clinical director of the Thoracic Oncology Program at Vanderbilt-Ingram Cancer Center, discusses data from an updated analysis of the phase 3 IMpower133 trial, which examined the first-line combination of atezolizumab (Tecentriq), carboplatin, and etoposide in small cell lung cancer (SCLC).

Results from an exploratory analysis of IMpower133 presented during the 2020 AACR Virtual Annual Meeting showed that the combination continued to improve overall survival (OS) compared with chemotherapy alone in the frontline treatment of patients with extensive-stage SCLC, regardless of PD-L1 and blood tumor mutational burden (TMB) status.

One important thing to remember withseveral trials evaluating checkpoint inhibitors, Horn notes, is that oftentimes investigators are focusing on the tail of the curve and trying to understand whether patients are experiencing long-term survival. With longer follow-up, results showed that the triplet regimen continued to have an OS benefit, at 12.3 months with a hazard ratio of 0.76. Additionally, the 18-month OS was found to be 13% higher in patients treated with the triplet versus those given chemotherapy alone, at 34% versus 21%.

Updated results related to PD-L1 expression and TMBand and how these factors might help to predict outcomes with checkpoint inhibitor therapies were also presented. In the original publication, investigators examined blood TMB using cutoffs of both 10 and 16 and found that this factor did not serve as a predictor of response or survival with checkpoint inhibitor therapy. A benefit was observed in patients with high TMB and low TMB, Horn concludes.

Videos

Leora Horn, MD, MSc, discusses data from an updated analysis of the phase 3 IMpower133 trial, which examined the first-line combination of atezolizumab (Tecentriq), carboplatin, and etoposide in small cell lung cancer.

Dr. Horn on Updated IMpower133 Data in Small Cell Lung Cancer

Leora Horn, MD, associate professor of medicine (hematology and oncology), assistant director, educator development program, clinical director, Thoracic Oncology, medical oncologist, Vanderbilt-Ingram Medical Center, discusses the FDA approval of atezolizumab (Tecentriq) for use in combination with bevacizumab (Avastin), carboplatin, and paclitaxel for the first-line treatment of patients with metastatic nonsquamous non—small cell lung cancer (NSCLC).

Leora Horn, MD, associate professor of medicine (hematology and oncology), assistant director, educator development program, clinical director, Thoracic Oncology, medical oncologist, Vanderbilt-Ingram Medical Center, discusses the FDA approval of atezolizumab (Tecentriq) for use in combination with bevacizumab (Avastin), carboplatin, and paclitaxel for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer. 

Dr. Horn on the FDA Approval of Atezolizumab Plus Bevacizumab and Chemotherapy in NSCLC

Leora Horn, MD, associate professor of medicine (hematology and oncology), assistant director, educator development program, clinical director, Thoracic Oncology, medical oncologist, Vanderbilt-Ingram Medical Center, discusses next steps with atezolizumab (Tecentriq) in small cell lung cancer (SCLC).

Data from the IMpower133 study presented at the 19th World Conference on Lung Cancer, and simultaneously published in the New England Journal of Medicine, showed that the addition of atezolizumab to standard carboplatin and etoposide in the frontline setting significantly prolonged survival in patients with extensive-stage SCLC. This regimen of atezolizumab plus chemotherapy may become the new frontline standard of care for patients with stage IV disease, Horn says.

Next steps are addressing patients who fail the atezolizumab regimen, explains Horn. Right now, the only option for these patients is topotecan, which has not shown much efficacy. There are other agents like lurbinectedin emerging in this space that might have an impact, though.

Leora Horn, MD, associate professor of medicine (hematology and oncology), assistant director, educator development program, clinical director, Thoracic Oncology, medical oncologist, Vanderbilt-Ingram Medical Center, discusses next steps with atezolizumab (Tecentriq) in small cell lung cancer.

Dr. Horn Discusses Next Steps With Atezolizumab in SCLC

Leora Horn, MD, associate professor of medicine (hematology and oncology), assistant director, educator development program, clinical director, Thoracic Oncology, medical oncologist, Vanderbilt-Ingram Medical Center, discusses selecting the necessary inhibitor for patients with 

-positive non—small cell lung cancer (NSCLC).

Horn says that in terms of efficacy, alectinib (Alecensa) is more effective than crizotinib (Xalkori) in the frontline setting. Ceritinib (Zykadia) resulted in better responses than chemotherapy, which is expected when comparing a targeted agent and chemotherapy, she adds.

Data also showed that ceritinib is more toxic than alectinib, suggesting that physicians should choose the latter in the first-line setting. Over time, she says, mechanisms of resistance will also come into play when deciding between these ALK inhibitors.

Overall survival is the key to deciding which drugs to use, Horn concludes.

Leora Horn, MD, associate professor of medicine (hematology and oncology), assistant director, educator development program, clinical director, Thoracic Oncology, medical oncologist, Vanderbilt-Ingram Medical Center, discusses selecting the necessary inhibitor for patients with ALK-positive non-small cell lung cancer.

Dr. Horn on Selecting Inhibitors for ALK+ NSCLC

Leora Horn, MD, associate professor of medicine (hematology and oncology), assistant director, educator development program, clinical director, Thoracic Oncology Program, medical oncologist, Vanderbilt-Ingram Center Center, discusses adverse event considerations for immunotherapy in lung cancer.

It still needs to be determined how different patients respond to immunotherapies, says Horn. PD-1 status does not seem to have an impact on adverse events. There also does not seem to be an association between adverse events and prior therapies. There has however, been more adverse events when agents have been combined, says Horn.

With chemotherapy, adverse events go away when the treatment is stopped. However, with immunotherapy the adverse events continue after the treatment is discontinued. 

Leora Horn, MD

Articles

Dr. Horn on Updated IMpower133 Data in Small Cell Lung Cancer

Dr. Horn on the FDA Approval of Atezolizumab Plus Bevacizumab and Chemotherapy in NSCLC

Dr. Horn Discusses Next Steps With Atezolizumab in SCLC

Dr. Horn on Selecting Inhibitors for ALK+ NSCLC

Dr. Leora Horn on Toxicities With Immunotherapy in Lung Cancer