Unmet Needs and Future Directions in ES-SCLC
Jared Weiss, MD, shares insight into current unmet needs in extensive-stage small cell lung cancer and provides advice to researchers about the importance of clinical trials studying differential treatments and biomarkers.
Jared Weiss, MD: We have an unmet need. What are the future directions that we can consider, and what advice can I offer for community oncologists treating extensive-stage small cell lung cancer? This is a bit of a tough question, because the greatest unmet need is that our treatments don’t last and they’re toxic. After a long time without improvements in survival, we have had legitimate gains in recent years. The addition of PD-L1 inhibition to chemotherapy improves survival of it. Trilaciclib decreases the toxicity of standard-of-care chemotherapy: carboplatin-etoposide; carboplatin, etoposide, and atezolizumab; or topotecan. It’s an unmet need to study it together with lurbinectedin. Lurbinectedin adds to our treatment armamentarium. In the combination comparative study it may not have improved survival, but I hope we can improve total patient outcomes by having an additional active drug in our armamentarium.
Frankly, community oncologists know how to care for extensive-stage small cell lung cancer. They’ve already integrated PD-L1 inhibition into their care, and they’re actively integrating trilaciclib. I don’t believe that community oncologists are the gap. The gap, or the unmet need, really falls on those of us in research. Where are we? TCGA [The Cancer Genome Atlas] transcription subtyping has shown us the diverse biology of small cell lung cancer, and I’m hopeful that it may ultimately lead to differential treatments. SLFN11 may prove to be our first biomarker. Multiple preserved neoantigens are being studied for BiTE [bispecific T-cell engager] and cellular therapeutics, most prominently DLL3 and GD2.
If I had to add 1 piece of advice for my community colleagues, it might be to consider trials for their patients. Small cell is a rough disease, and standard treatments don’t offer as much as we’d like for our patients. The limitations of our current standard therapies should lower the bar for offering trials to every patient. Thank you for your kind attention.
Transcript edited for clarity.
Case: A 64-Year-Old Woman with Small-Cell Lung Cancer
Initial Presentation
- A 64-year-old woman presented with a persistent cough, chest discomfort, fatigue and unintended weight loss
- PMH: osteoporosis, hysterectomy at age 60, prediabetic managed with diet and exercise
- SH: 45-pack year smoking history; drinks alcohol 1-2/month socially
- PE: Decreased breath sounds in left lung, wheezing on auscultation, axillary lymph node enlargement
Clinical Workup
- Labs: serum Na 132 mEq/L; ALT 54 IU/L; AST 58 IU/L; all others WNL
- Axillary lymph node biopsy revealed small cell carcinoma
- Chest/abdomen/pelvic CT showed a 7.2 cm mass above the diaphragm, a small contralateral lung nodule and evidence of invasion into the left side of the pericardium
- PET scan showed activity in the left lung above the diaphragm, mediastinum and small hypermetabolic activity in the surrounding area
- Contrast‐enhanced MRI of the head was negative for brain metastases
- Stage IV small-cell lung cancer; ECOG PS 0
Treatment
- Initiated carboplatin + etoposide + atezolizumab for 4 cycles; followed with atezolizumab as maintenance therapy
Follow-up
- 7 months after starting treatment she complained of fatigue, shortness of breath, right upper quadrant pain and back pain
- CT scan showed hematogenous metastases in the liver
- Initiated lurbinectedin 3.2 mg/m2 IV q21 days
