ATLANTIS Trial Misses Primary End Point in Patients With SCLC

Treatment with lurbinectedin and doxorubicin missed the prespecified end point of overall survival in patients with small cell lung cancer who progressed after 1 prior platinum therapy.

Treatment with lurbinectedin (Zepzelca) and doxorubicin missed the prespecified end point of overall survival (OS) in patients with small cell lung cancer (SCLC) who progressed after 1 prior platinum therapy, according to a press release from Jazz Pharmaceuticals and PharmaMar.1

In the phase 3 ATLANTIS trial (NCT02566993), the combination of lurbinectedin and doxorubicin was compared with physician’s choice of topotecan or cyclophosphamide/doxorubicin/vincristine (CAV) in 613 patients randomized 1:1. In the intent-to-treat population, although OS was not met, the secondary end points and subgroup analyses favored the investigational combination.

Secondary end points included the difference in OS for the 2 arms; OS and progression-free survival (PFS) in patients with or without central nervous system involvement; and PFS, antitumor activity defined by objective response rate, and duration of response all per independent review committee.

“Historically, patients with relapsed SCLC often face difficult odds due to the aggressive nature of the disease and they have had very limited treatment options,” stated Alberto Chiappori, MD, from the H. Lee Moffitt Cancer Center and Research Institute and ATLANTIS study investigator, in a press release. “As a physician treating patients with SCLC, I’m confident in lurbinectedin as an effective new option in this traditionally challenging therapeutic area.”

Lurbinectedin and doxorubicin did not have any adverse effects on patient’s OS. There were no new safety signals for the combination and the safety data observed in ATLANTIS were consistent with the known safety profile of lurbinectedin monotherapy. Grade 3 or more drug-related adverse events (AEs), hematologic AEs, deaths due to AEs, dose reductions and treatment discontinuations due to AEs were all more favorable in the combination versus the control arm.

“Bringing Zepzelca to the U.S. market earlier this year alongside our partner, PharmaMar, was an important advance for adults with metastatic SCLC, an aggressive disease with a historically poor prognosis,” said Robert Iannone MD, MSCE, executive vice president, research and development of Jazz Pharmaceuticals, in a statement. “While the combination of lurbinectedin and doxorubicin did not achieve the primary end point in this study, the overall results support the activity and tolerability of lurbinectedin in this line of therapy. We look forward to the further development of lurbinectedin in SCLC and other tumors, both as monotherapy and in combination.”

For patients on the trial randomized to the experimental arm, lurbinectedin was given at 2 mg/m2. This was lower than the FDA approved dose of 3.2 mg/m2. Patients were stratified by chemotherapy free interval, ECOG performance status of 0 or 1 to 2, central nervous system involvement, PD-1, PD-L1, and investigator preference of topotecan and CAV.

“We remain committed to improving outcomes for patients with metastatic small cell lung cancer where there is a high unmet medical need; we continue to evaluate the safety and efficacy of lurbinectedin in SCLC and other tumors. The drug’s activity in this disease and setting has been reinforced in this trial,” said Luis Mora, managing director, oncology business unit, PharmaMar, in a statement.

Lurbinectedin received accelerated approval from the FDA earlier in 2020 for adult patients with metastatic SCLC with disease progression on or after platinum0based chemotherapy after it demonstrated effaceable overall response rate and duration of response in an open-label trial.2


1. Jazz Pharmaceuticals and PharmaMar announce results of ATLANTIS phase 3 study evaluating Zepzelca™ in combination with doxorubicin for patients with small cell lung cancer following one prior platinum-containing line. News release. Jazz Pharmaceuticals. December 3, 2020. Accessed December 3, 2020.

2. FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. News release. FDA. June 16, 2020. Accessed December 3, 2020.