Nondriver Adenocarcinoma: Determining Therapy

ASCO 2020 Data Update: CheckMate 227

CheckMate-227 Regimen Safety Profile 

Recent Combination Approval: CheckMate-9LA Regimen 

CheckMate-9LA: Histology and Frontline Impact 

Frontline PD-L1 Monotherapy: KEYNOTE-042 and IMpower110 

PD-L1 Combination Therapy Clinical Trials 

CheckMate 817 Overview

Squamous Cell Frontline Therapy: IMpower 131, KEYNOTE-407

NSCLC Management: Second-Line Options

Videos

I/O-Based Therapy in Non–Small Cell Lung Cancer

Neal E. Ready, MD, PhD, professor of medicine, Duke University School of Medicine, member, Duke Cancer Institute, discusses emerging treatment approaches in small cell lung cancer (SCLC).

DLL3 is a potentially important target in SCLC as it is expressed in about 70% of cases. Importantly, DLL3 is not typically expressed on normal cells. An antibody-drug conjugate called rovalpituzumab tesirine (Rova-T) has shown activity when targeted against DLL3. However, it has yet to receive regulatory approval because it has modest activity and a significant toxicity profile, says Ready. Nonetheless, the agent has validated DLL3 as a target.

Several pharmaceutical companies are now looking at targeting DLL3 with bispecific T-cell engager antibody approaches. DLL3 may also serve as a good target for CAR T-cell therapy, an approach that has shown activity in some leukemias and has become standard therapy in some lymphomas, explains Ready.

PARP is also under investigation as a potential target since it is an important enzyme in DNA repair and therein cancer cell growth and survival; it may also be related to the development of antigens that the immune system can respond against. The combination of PARP inhibitors and chemotherapy has shown promise, but not enough to warrant an approval in all comers, says Ready. Additional research is looking at PARP inhibitors with temozolomide (Temodar), and there is preclinical research evaluating the use of PARP inhibitors with immunotherapy.

Dr. Ready on Promising Treatment Approaches in SCLC

Neal E. Ready, MD, PhD, professor of medicine, Duke University School of Medicine, member, Duke Cancer Institute, discusses the benefit of PD-L1 inhibition in small cell lung cancer (SCLC).

Immunotherapy activates the body’s own immune system to fight the cancer, Ready says. Traditionally, there had only been anecdotal success with this therapy in the form of vaccines as well as other approaches across tumor types. Over the last 2 decades, basic science has indicated that there are checkpoints on immune cells that allow the tumor to turn off the immune system. The use of checkpoint inhibitors such as the PD-L1 inhibitor atezolizumab (Tecentriq) are ways in which to overcome this.

In extensive-stage SCLC, atezolizumab is being combined with chemotherapy. Data from the pivotal IMpower133 study showed that chemoimmunotherapy improved overall survival for these patients, notably extending survival beyond 1 and 2 years for select patients.

Neal E. Ready, MD, PhD, professor of medicine, Duke University School of Medicine, member, Duke Cancer Institute, discusses the benefit of PD-L1 inhibition in small cell lung cancer.

Neal E. Ready, MD, PhD, Duke University Medical Center

Articles

I/O-Based Therapy in Non–Small Cell Lung Cancer

Dr. Ready on Promising Treatment Approaches in SCLC

Dr. Ready on the Benefit of PD-L1 Inhibition in SCLC