The ATLANTIS Study of Lurbinectedin/Doxorubicin

EP: 1.Case Overview: A 64-Year-Old Woman With ES-SCLC

EP: 2.First-Line Treatment Options for ES-SCLC

EP: 3.Second-Line Treatment After Maintenance Immunotherapy

EP: 4.Safety and Efficacy of Lurbinectedin in Solid Tumors

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EP: 5.The ATLANTIS Study of Lurbinectedin/Doxorubicin

EP: 6.Unmet Needs and Future Directions in ES-SCLC

Jared Weiss, MD: Let’s turn our attention now to the ATLANTIS study. ATLANTIS was a randomized study of lurbinectedin in combination with doxorubicin in relapsed small cell lung cancer. This combination was compared in randomized fashion with the standard of care, defined as dealer’s choice of CAV [cyclophosphamide, doxorubicin, vincristine] or topotecan. The dose of lurbinectedin in this combination trial was 2.3 mg/m². The combination with doxorubicin left many doctors, myself included, scratching our heads from a clinical perspective. Adriamycin [doxorubicin] is a fairly hated drug, sometimes nicknamed the red devil, but there were preclinical data to support this combination. Unfortunately, the combination of doxorubicin and lurbinectedin at a dose of 2.3 mg/m² failed to improve survival compared with CAV [cyclophosphamide, doxorubicin, vincristine] or topotecan. Why did this happen? One possibility is dosage. The dose in the combination was 2.3 mg/m². In the basket trial, it was 3.2 mg/m².

In evaluating this possibility, the companies put out a poster [at the International Association for the Study of Lung Cancer World Conference on Lung Cancer] that looked at the relationship between AUC [area under the curve] dose exposure and both response rate and toxicity. It showed that when the exposure was ideal, the response rate was quite a bit better and the toxicity more limited. That argues that the dose really might have mattered. Unfortunately, the AUC exposure was fairly broad at that 3.2 mg/m² dosing in the basket trial. Still, it does make common sense that if the patients are at 3.2 mg instead of 2.3 mg, you’re going to have more patients at an adequate dose. Where does that leave us? Unless the FDA says otherwise, lurbinectedin remains a second-line option. In my practice, it remains the preferred option in second line, but in reflecting, we still have a very real unmet need.

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