A very complex genetic landscape of SCLC accounts for its resistance to conventional therapy and a high recurrence rate; however, at the same time this complexity can form the basis for effective targeted therapy for the disease. One of the major limitations to the development of targeted therapies in SCLC is limited availability of tissue owing to small tissue samples and frequent presence of significant necrosis in the samples. In recent years, several different therapeutic strategies and targeted agents have been under investigation for their potential role in SCLC. Several of them, including EGFR TKIs, BCR-ABL TKIs, mTOR inhibitors, and VEGF inhibitors, have been unsuccessful in showing a survival advantage in this disease. Several others including PARP inhibitors, cellular developmental pathway inhibitors and antibody drug conjugates are being tested. A phase I study of veliparib combined with cisplatin and etoposide in patients with previously untreated extensive-stage SCLC demonstrated complete response in 14.3%, partial response in 57.1%, and stable disease in 28.6% of patients with acceptable safety profile . So far, none of these agents are approved for use in SCLC and the majority are in early phase clinical trials .
One of the emerging targets in the treatment of SCLC is DLL3. DLL3 is expressed on > 80% SCLCL tumor cells and cancer stem cells. Rovalpituzumab tesirine (ROVA-T) is an antibody drug conjugate consisting of humanized anti-DLL3 monoclonal antibody linked to SC-DR002, a DNA-crosslinking agent. A phase I trial of ROVA-T in patients with relapsed SCLC after 1 or 2 prior lines of therapies reported a response rate of 31% in patients with DLL3 expression of ≥ 50%. The median duration of response and mPFS were 4.6 months . ROVA-T is currently in later phases of clinical trials and has a potential to serve as one of the options for patients with extensive-stage disease after disease progression on platinum-based therapy.
For patients undergoing treatment for limited-stage SCLC, response assessment with contrast-enhanced CT of the chest/abdomen should be performed after completion of 4 cycles of chemotherapy and thoracic radiation. The surveillance guidelines consist of history, physical exam, and imaging every 3 months during 1st 2 years, every 6 months during the 3rdyear, and annually thereafter. If PCI is not performed, brain MRI or contrast enhanced CT scan should be performed every 3 to 4 months during the first 2 years of follow-up. For extensive-stage disease, response assessment should be performed after every 2 cycles of therapy. After completion of therapy, history, physical exam, and imaging should be done every 2 months during the 1st year, every 3 to 4 months during year 2 and 3, every 6 months during years 4 and 5, and annually thereafter. Routine use of PET scan for surveillance is not recommended. Any new pulmonary nodule should prompt evaluation for a second primary lung malignancy. Finally, smoking cessation counseling is an integral part of management of any patient with SCLC and should be included with every clinic visit.
Corresponding author: Hirva Mamdani, MD, Karmanos Cancer Institute, 4100 John R, Detroit, MI 48201, email@example.com.
Financial disclosures: None.