Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial

Aix, Santiago Ponce; Ciuleanu, Tudor; Navarro, Alejandro; Cousin, Sophie; Bonanno, Laura; Smit, Egbert F.; Chiappori, Alberto; Olmedo, María Eugenia; Horváth, Ildikó; Grohé, Christian; Farago, Anna F.; López-Vilariño, José Antonio; Cullell-Young, Martín; Nieto, Antonio; Vasco, Noelia; Gómez, Javier; Kahatt, Carmen; Zeaiter, Ali; Carcereny, Enric; Roubec, Jaromı́r; Syrigos, Konstantinos; Lo, Gregory; Barneto, I.; Pope, Anthony; Sánchez, Amparo Martínez; Kattan, Joseph; Zarogoulidis, Konstantinos; Waller, Cornelius F.; Bischoff, Helge; Juan-Vidal, O.; Reinmuth, Niels; Dómine, Manuel; Paz‐Ares, Luis

doi:10.1016/s2213-2600(22)00309-5

Cited by 57 publications

(39 citation statements)

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“…As such, future studies may also determine whether SSTR-targeted molecular imaging may allow to initiate combined-therapeutic strategies to achieve synergistic, tumor-targeting effects, for example, PRRT plus lurbinectedin. In this regard, such a “dual hit” of selective inhibition of SSTR and oncogenic transcription may then also prolong survival, which is currently not achieved by those therapies alone 11,17 . Limitations of the present investigation include the low number of analyzed subjects, in particular for the different subgroups.…”

Section: Discussionmentioning

confidence: 93%

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Somatostatin Receptor-Directed PET/CT for Therapeutic Decision-Making and Disease Control in Patients Affected With Small Cell Lung Cancer

et al. 2023

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BackgroundSomatostatin receptor (SSTR)–targeted PET/CT is used for patients affected with small cell lung cancer (SCLC), but the clinical impact has not been elucidated yet. We aimed to determine whether SSTR PET/CT can trigger relevant therapeutic management changes in patients with SCLC and whether those modifications achieve disease control and are associated with prolonged survival.MethodsOne hundred patients with SCLC received SSTR PET/CT. In a retrospective setting, we evaluated the diagnostic performance of PET versus CT and compared therapies before and after PET/CT to determine the impact of molecular imaging on treatment decision. We also determined the rate of disease control after therapeutic modifications and assessed survival in patients with and without changes in the therapeutic regimen.ResultsRelative to CT, SSTR PET alone was superior for assessing bone lesions in 19 of 39 instances (49%). Treatment was modified in 59 of 100 (59%) after SSTR PET/CT. Forty of 59 (74.6%) received systemic treatment after hybrid imaging, with the remaining 15 of 59 (25.4%) scheduled for nonsystemic therapy. In the latter group, 13 of 15 (86.7%) received local radiation therapy or active surveillance (2/15 [13.3%]). Individuals scheduled for systemic treatment after imaging received peptide receptor radionuclide therapy (PRRT) in 28 of 44 (63.6%), followed by chemotherapy in 10 of 44 (22.7%), change in chemotherapy regimen in 3 of 44 (6.8%), and initiation of tyrosine kinase inhibitor in the remaining 3 of 44 (6.8%). Among patients with modified treatment, follow-up was available in 53 subjects, and disease control was achieved in 14 of 53 (26.4%). However, neither change to systemic treatment (155 days; hazard ratio, 0.94; 95% confidence interval, 0.53–1.67) nor change to nonsystemic treatment (210 days; hazard ratio, 0.67; 95% confidence interval, 0.34–1.34) led to a prolonged survival when compared with subjects with no change (171 days, P ≥ 0.22, respectively).ConclusionsIn patients with SCLC, SSTR-targeted hybrid imaging provides complementary information on the disease status. PET/CT led to management changes in 59% (mainly PRRT), achieving disease control in >26%. The high fraction of patients scheduled for PRRT may lay the foundation for combination strategies to achieve synergistic antitumor effects, for example, by combining PRRT plus recently introduced RNA polymerase II inhibitors.

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Section: Discussionmentioning

confidence: 93%

“… 2 , 16 In this regard, achieved synergistic antitumor effects may then also increase survival, which is currently not accomplished by respective monotherapies. 11 , 17 …”

Section: Discussionmentioning

confidence: 99%

Somatostatin Receptor-Directed PET/CT for Therapeutic Decision-Making and Disease Control in Patients Affected With Small Cell Lung Cancer

et al. 2023

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“…In patients with a CTFI of 180 days or more, the median OS was 16.2 months (95% CI, 9.6 to not reached) . In the phase 3 ATLANTIS trial, lurbinectedin-doxorubicin combination treatment did not improve median OS vs topotecan or CAV (8.6 vs 7.6 months; HR, 0.97; 95% CI, 0.82-1.15), although improvements in PFS (HR, 0.81; 95% CI, 0.69-1.00; P = .04) and hematologic toxic effects were observed. A phase 1b/2 study reported a 62% ORR for lurbinectedin-irinotecan in patients with pretreated SCLC, with moderate hematologic toxic effects, and is the basis for the ongoing phase 3 LAGOON trial .…”

Section: Biologic Characteristics and Pathophysiologymentioning

confidence: 94%

Emerging Strategies for the Treatment of Small Cell Lung Cancer

Petty

Paz‐Ares

2023

JAMA Oncol

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ImportanceSmall cell lung cancer (SCLC) is an aggressive disease that is characterized by rapid growth and the early development of metastases. Patients typically respond to initial chemotherapy but quickly experience relapse, resulting in a poor long-term outcome. Therapeutic innovations that substantially improve survival have historically been limited, and reliable, predictive biomarkers are lacking.ObservationsThis review examines the biologic characteristics of SCLC, the current treatment landscape, and ongoing efforts to identify novel therapeutic targets. Ongoing research has advanced the understanding of molecular categories and the immunologic microenvironment of SCLC, which in turn has helped improve disease classification and staging. Recently, immunotherapy-based regimens have become available for the management of SCLC, with 2 programmed cell death 1 ligand 1 inhibitors approved in combination with chemotherapy for first-line treatment of extensive-stage disease. For second-line treatment, a novel alkylating agent, lurbinectedin, which inhibits oncogenic transcription, has been approved for use in patients with metastatic SCLC. Furthermore, a wide variety of therapies and innovative combination regimens are being continuously evaluated. Potential therapeutic strategies, including aurora kinase A inhibitors, polyadenosine diphosphate-ribose polymerase inhibitors, ataxia telangiectasia and Rad3-related inhibitors, cyclin-dependent kinase 7 inhibitors, delta-like protein 3 agents, antiganglioside agents, CD47 inhibitors, and lysine-specific histone demethylase 1a inhibitors, are also being examined.Conclusions and RelevanceTherapeutic optimization of SCLC remains a challenge, but recent trial results and drug approvals are encouraging. Advances in research have revealed critical information regarding biologic characteristics of the disease, which may lead to the identification of vulnerabilities and the development of new therapies. Further research focused on identifying biomarkers and evaluating innovative therapies will be paramount to improving treatment outcomes for patients with SCLC.

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“…For NSCLC patients, the objective response rate of chemotherapy combined with ICIs is higher than that of ICIs alone [ 8 ]. A clinical trial of 613 patients with small cell lung cancer showed that lurbinectedin, a second-line drug, combined with doxorubicin did not improve the prognosis of patients, and combined treatment with ICIs may be a new starting point [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Risk score = LncRNAs associated with doxorubicin metabolism can be used as molecular markers for immune microenvironment and immunotherapy in non-small cell lung cancer

Lin

Zhang

Kong³

et al. 2023

Heliyon

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Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial

Cited by 57 publications

References 24 publications

Somatostatin Receptor-Directed PET/CT for Therapeutic Decision-Making and Disease Control in Patients Affected With Small Cell Lung Cancer

Somatostatin Receptor-Directed PET/CT for Therapeutic Decision-Making and Disease Control in Patients Affected With Small Cell Lung Cancer

Emerging Strategies for the Treatment of Small Cell Lung Cancer

Risk score = LncRNAs associated with doxorubicin metabolism can be used as molecular markers for immune microenvironment and immunotherapy in non-small cell lung cancer

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