Analyzing the Role of Topotecan and Lurbinectedin in Small Cell Lung Cancer
Dr Ticiana Leal, MD, discusses the role of topotecan and lurbinectedin as novel agents in second-line therapy for small cell lung cancer.
Ticiana Leal, MD: In terms of when you move on and what you move on to as a second-line strategy, if your patient is not a candidate for rechallenge because they are considered platinum resistant or because they have had significant prior toxicities to their regimen in the frontline setting when they used the platinum-etoposide, then we would move on to another agent. Our options at this point include topotecan as well as a new agent that was recently approved called lurbinectedin.
In terms of which agent to use, lurbinectedin is very well positioned to be our next strategy. It has a different mechanism of action. It’s a novel agent that was approved by the FDA in an accelerated fashion, and it’s a selective inhibitor of oncogenic transcription. It is a regimen that was recently approved that we started using in the clinical setting.
This agent was approved based on a global, multicenter, open-label phase 2 basket trial that included a cohort of patients with previously treated small cell lung cancer. In this trial, patients who had 1 prior line of platinum therapy—they could have received 1 prior immunotherapy agent—received lurbinectedin as a single agent for small cell lung cancer. The primary end point of this study was overall response rate, and this study did meet the overall response rate criteria that was defined statistically in the study.
Importantly, they actually treated 105 patients in the study. All these patients were previously treated. The overall response rate for patients in the second-line setting in this study was about 45% in the sensitive population and 22% in the resistant population, which is promising when you consider our historical controls. The resistant population especially shows a glimmer of hope given that the response rate with topotecan is about 5%. In the overall population, the response rate was about 35%. Importantly, they also had a duration of response that was considered promising in the order of 5 months. The median overall survival with lurbinectedin in this study was about 9.3 months in this previously treated population. The median overall survival was slightly better in the sensitive population in the order of 10 months.
This was a regimen that was studied in an initial study but led to FDA approval. It’s rolled out already to the community sites. Academic sites are also experienced with lurbinectedin to date with the number of patients we’ve treated. It has been favorable in the sense that it has been a regimen that has manageable adverse effects and has mirrored what we saw in this phase 2 study.
The main adverse effects of lurbinectedin have been related to myelosuppression. The main episodes we’re seeing that were more severe in terms of grade 3/4 events was neutropenia, but the number of episodes of febrile neutropenia was substantially lower. Certainly, you also see anemia and thrombocytopenia. About 20% of the patients did require G-CSF [granulocyte colony-stimulating factor] use in the trial because of myelosuppression.
Other potential adverse effects that are seen in 20% or greater of patients include fatigue, nausea, decreased appetite, elevation in LFTs [liver function tests], and potentially elevation in both creatinine and glucose.
Overall, the regimen seems to be well tolerated in this patient population and hasn’t shown any significant signals of prohibitive toxicity.
Transcript edited for clarity.
Case: A 61-Year-Old Man With Small-Cell Lung Cancer
Initial Presentation
- A 61-year-old man presented with a cough, fatigue, progressive shortness of breath
- PMH: unremarkable
- SH: 25-pack year smoking history; social alcohol use
- PE: Right lower lobe wheezing on auscultation, axillary lymph node enlargement
Clinical Workup
- Labs: WNL
- Axillary lymph node biopsy revealed small cell carcinoma
- Chest/abdomen/pelvic CT showed a 7.1 cm mediastinal conglomerate mass, with invasion into the right main and lobar pulmonary arteries; 2 small left pulmonary nodules; hypermetabolic axillary lymph node
- PET scan showed large focal hypermetabolic activity in the mediastinum and small hypermetabolic activity in the surrounding area
- Contrast‐enhanced MRI of the head showed no 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 he complained of shortness of breath, right upper quadrant pain and back pain
- CT showed hematogenous metastases in the liver and right adrenal gland
- Initiated lurbinectedin 3.2 mg/m2 IV q21 Days
