A 64-Year-Old Woman With Extensive-Stage Small Cell Lung Cancer - Episode 5
Expert oncologist Jared Weiss, MD, considers safety and efficacy data from the ATLANTIS study of lurbinectedin in combination with doxorubicin in relapsed small cell lung cancer.
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