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 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.