Safety and Efficacy of Lurbinectedin in Solid Tumors
Thought leader in lung cancer, Jared Weiss, MD, reviews safety and efficacy data from the phase 2 basket trial of lurbinectedin in selected advanced solid tumors.
Jared Weiss, MD: This patient was treated with lurbinectedin. Let’s look at trial design, efficacy, and safety results from the phase 2 basket trial that led to this approval. This was 105 patients with extensive-stage small cell [lung cancer] in second line taken from a larger-basket trial. The response rate was 35% overall; 22% in those with a chemotherapy-treatment-free interval of less than 90 days, and 45% in chemotherapy-treatment-free interval of greater than 90 days. Two-thirds of patients had response to prior chemotherapy as you’d expect, since the chemotherapy-treatment-free interval had to be at least 30 days and because it’s small cell. PFS [progression-free survival] was 3.5 months overall, 2.6 months in the chemotherapy-refractory patients, and 4.6 months in those who were sensitive. Overall survival was also different among these groups; overall was 9.3 months, but in those with the short chemotherapy-treatment-free interval, it was 5 months. In those with the long chemotherapy-treatment-free interval, it was 12 months.
As we might expect, the toxicity was largely hematologic, but it was mostly lower grade. Anemia happened in almost every patient, but only 9% at grade 3, no grade 4. Leukopenia happened in half of patients at grade 1 and 2, and 29% of patients in grade 3 and 4. Neutropenia occurred in 26% of patients at grade 1 or 2, 21% at grade 3, and 25% at grade 4. Thrombocytopenia occurred in 37% at grades 1 and 2, and 3% at grade 3. The other major toxicities were also largely laboratory related as opposed to end organ. In terms of things patients feel more directly, as you would expect, there was some nausea and fatigue with the cytotoxic agent, but very few at high grade. The same can be said for decreased appetite, vomiting, and diarrhea. My experience, with the extremely important caveat that it’s a small number of patients, is not quite as favorable as the basket trial. I’ve had a little bad luck with patients not responding and a tolerability profile may be a little worse than the toxicity tables from the trial would suggest, but I highly caution against substituting experience with a small number of patients against the larger number in a controlled trial with careful data gathering.
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
