Chandra P. Belani, MD, deputy director, Penn State Hershey Cancer Institute, Miriam Beckner Distinguished Professor of Medicine, Penn State Hershey College of Medicine, discusses atezolizumab in non-small cell lung cancer (NSCLC).

The immunotherapy agent has been studied in both the BIRCH and POPLAR trials. In the BIRCH study, atezolizumab met its primary endpoint, demonstrating a 27% objective response rate in patients whose disease had progressed on prior medicines and also expressed the highest levels of PD-L1.

In the POPLAR study, atezolizumab showed a statistically significant survival benefit compared to docetaxel in recurrent NSCLC patients who had had failed prior chemotherapy. There was an approximant 3-month difference in overall survival with atezolizumab compared to docetaxel.

PD-L1 seems to be a predictor of response and activity in NSCLC for atezolizumab, says Belani.

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Dr. Chandra Belani on Atezolizumab in NSCLC

Chandra P. Belani, MD, Miriam Beckner Distinguished Professor of Medicine, Penn State Milton S. Hershey Medical Center, deputy director, Penn State Hershey Cancer Institute, discusses how the FDA approval of nivolumab (Opdivo) has impacted the treatment paradigm of non—small cell lung cancer (NSCLC).

Nivolumab is approved in NSCLC for patients with both squamous and nonsquamous histologies, Belani explains. The basis of the approval for squamous patients is on data from the phase III CheckMate-057 study, which demonstrated a 3.6-month overall survival benefit with nivolumab versus docetaxel, regardless of staining for PD-1 expression.

In the nonsquamous population, a 2.8-month improvement was demonstrated, Belani adds. Nivolumab can be administered to all nonsquamous patients with NSCLC, an indication that it was approved for in October 2015, in the second-line setting after failure on chemotherapy.

Chandra P. Belani, MD, Miriam Beckner Distinguished Professor of Medicine, Penn State Milton S. Hershey Medical Center, deputy director, Penn State Hershey Cancer Institute, discusses how the FDA approval of nivolumab (Opdivo) has impacted the treatment paradigm of nonâ€“small cell lung cancer (NSCLC).


Dr. Belani on Impact of Nivolumab's Approval in NSCLC

Chandra P. Belani, MD, deputy director, Penn State Hershey Cancer Institute, Miriam Beckner Distinguished Professor of Medicine, Penn State Hershey College of Medicine, discusses the benefits of immunotherapy for lung cancer.

Checkpoint inhibitors targeting PD-1 and PD-L1 have started to show beneficial effects in patients with non-small cell lung cancer, says Belani. The drugs that target PD-1 and PDL-1 lead to increases in the patients. own tumor immunity. Not all patients respond, but there may be a biomarker for treatment to determine when to utilize these therapies.

Dr. Belani on PD-1 Inhibitors for Non-Small Cell Lung Cancer 

Chandra P. Belani, MD, deputy director, Penn State Hershey Cancer Institute, Miriam Beckner Distinguished Professor of Medicine, Penn State Hershey College of Medicine, discusses CO-1686, which is currently being studied for the treatment of non-small cell lung cancer (NSCLC).

Belani says CO-1686 targets the EGFR mutation as well as T790M mutations, which causes resistance to EGFR-directed therapies. Belani says this drug has not reached its maximum tolerated dose. Doses up to 900mg BID have been given during the study.

Halfway through the study, the formation was changed because the hydrobromide salt tablet formulation of the agent was found to be more effective pharmaceutically and did not have any effect on wild-type EGFR. Belani says this reduced the side effects of rash and diarrhea.

The impressive activity of this agent has been seen in patients with T790M mutations, with an overall response rate of 67%, Belani says.

Belani says there is currently a phase I study of this agent in the Japanese population and more data will be available in the near future. 

Chandra P. Belani, MD, discusses CO-1686, which is currently being studied for the treatment of non-small cell lung cancer.

Dr. Belani Discusses Treating NSCLC with CO-1686

Chandra P. Belani, MD, Deputy Director, Penn State Hershey Cancer Institute, Miriam Beckner Distinguished Professor of Medicine, Penn State Hershey Medical Center & College of Medicine, discusses the multicenter Lung Cancer Mutation Consortium (LCMC) study that sought to detect driver mutations in patients with non-small cell lung cancer (NSCLC).

The detection of various driver mutations could help compartmentalize overall NSCLC. Determining the exact mutation responsible for tumor growth could help identify the patients that are eligible to receive specific targeted agents.

The LCMC study found that approximately 54% of patients with NSCLC have some form of a mutation. The major abnormalities include mutations in 

 rearrangement. Most of these alterations appear to be mutually exclusive; very few tumors have dual or triple abnormalities.

According to Belani this research only scratches the surface of the NSCLC biology. Subsequent discoveries will show that NSCLC is heterogeneous; further aberrations will be discovered as more research is completed.

Dr. Chandra Belani from Penn State Hershey Cancer Institute Discusses Driver Mutations in NSCLC

Dr. Belani Discusses Driver Mutations in NSCLC

Chandra P. Belani, MD, Deputy Director, Penn State Hershey Cancer Institute, Miriam Beckner Distinguished Professor of Medicine, Penn State Hershey Medical Center & College of Medicine, discusses recent changes to adjuvant therapy for non-small cell lung cancer (NSCLC).

Adjuvant therapy is the current standard of care for patients with resectable NSCLC. Various trials have suggested that the absolute improvement in overall survival from adjuvant treatment is 4.1-15%. Most practitioners assume an approximate 7-8% overall improvement.

Recent trials have suggested that new combinations such as cisplatin and pemetrexed have an equivalent effect, and may be more feasible, than the current standard of cisplatin plus vinorelbine or etoposide, which has recently been the focus of multiple studies.

While a comparison of these standards is not currently needed it has resulted in a paradigm shift in adjuvant care for early-stage resectable NSCLC, with the exception of patients with stage IA-IB that measures less than 4 cm.

Dr. Chandra Belani, from the Penn State Hershey Cancer Institute, Discusses NSCLC Adjuvant Therapy

Chandra P. Belani, MD

Articles

Dr. Chandra Belani on Atezolizumab in NSCLC

Dr. Belani on Impact of Nivolumab's Approval in NSCLC

Dr. Belani on PD-1 Inhibitors for Non-Small Cell Lung Cancer

Dr. Belani Discusses Treating NSCLC with CO-1686

Dr. Belani Discusses Driver Mutations in NSCLC

Dr. Belani Discusses NSCLC Adjuvant Therapy