1529PD - Activity of lurbinectedin as single agent and in combination in patients with advanced small cell lung cancer (SCLC)

Date 11 September 2017
Event ESMO 2017 Congress
Session Non-metastatic NSCLC and other thoracic malignancies
Topics Anti-Cancer Agents & Biologic Therapy
Small-Cell Lung Cancer
Lung and other Thoracic Tumours
Presenter Mª Eugenia Olmedo Garcia
Citation Annals of Oncology (2017) 28 (suppl_5): v539-v542. 10.1093/annonc/mdx386
Authors M.E. Olmedo Garcia1, M. Forster2, E. Calvo3, V. Moreno4, M.P. Lopez Criado5, J.A. Lopez-Vilarino de Ramos6, C. Kahatt6, P. Lardelli6, X.E. Luepke-Estefan6, A. Soto-Matos6
  • 1Oncologia, Hospital Universitario Ramon y Cajal, 28034 - Madrid/ES
  • 2Oncology, University College London Hospital, WC1E6BT - London/GB
  • 3Oncology, Centro Integral Oncologico Clara Campal - Hospital Madrid-Norte San Chinarro, 28050 - Madrid/ES
  • 4Oncology, Fundacion Jimenez Diaz, 28040 - Madrid/ES
  • 5Oncology, MD Anderson Cancer Center Center, 28033 - Madrid/ES
  • 6Clinica, PharmaMar, Madrid/ES

Abstract

Background

Lurbinectedin (PM01183, L) is a novel anticancer drug that inhibits activated transcription, induces DNA double-strand breaks generating apoptosis, and modulates tumor microenvironment. Relapsed SCLC still remains an unmet medical need.

Methods

Antitumor activity and safety of Lurbinectedin in SCLC was reviewed in three clinical trials (n = 83 patients): two phase I in combination with doxorubicin (L+DOX; n = 48, two cohorts) or paclitaxel (L+TAX, n = 7), and a phase II single-agent basket trial (n = 28).

Results

Median age was similar in these three studies. CNS was involved in 33% (L+DOX cohort A), 4% (L+DOX cohort B), 29% (L+TAX) and 0% of patients (L alone). Patients with sensitive disease were 52%, 64%, 71% and 71%, respectively. Activity was seen in the three studies (see Table). The most reported toxicity was hematological (G3-4 neutropenia/thrombocytopenia/febrile neutropenia: L+DOX Cohort A 96%/34%/34%; L+DOX Cohort B 89%/11%/14%; L+TAX 86%/0%/14%, and L alone 32%/4%/4%). Non-hematological toxicity was mainly G1-2 and included fatigue, nausea/vomiting, and transaminase increase.

Conclusions

Lurbinectedin shows activity as a single agent and in combination with other agents (DOX and TAX) in relapsed SCLC. Results were remarkable in terms of PFS, DCR and duration of response, especially in platinum-sensitive SCLC. Toxicity mainly consisted of transient myelosuppression, which was manageable with dose reductions and G-CSF use. A randomized Phase III with L+DOX is ongoing (ATLANTIS Study).Table:

1529PD

Response Evaluable patientsLurbinectedin+DOX (q3wk)Lurbinectedin + TAX (q3wk)Lurbinectedin alone (q3wk)
Cohort A L 3-5 mg FD D1 + DOX 50 mg/m2 D1 (n = 21)Cohort B L 2 mg/m2 D1 + DOX 40 mg/m2 D1 (n = 27)L 2.2 mg/m2 D1 + TAX 80 mg/m2 D1 & D8 (n = 7)L 3.2 mg/m2 D1 (n = 24)
CR2 (10%)1 (4%)1 (14%)
PR12(57%)9 (33%)4 (57%)6 (25%)
ORR14 (67%)10 (37%)5 (71%)6 (25%)
SD3 (14%)9 (33%)12 (50%)
PD4 (19%)8 (30%)2 (29%)6 (25%)
DCR17 (81%)19 (70%)5 (71%)18 (75%)
DOR (mo)4.53.72.36.2+
PFS (mo) Platinum-sensitive5.85.74.83.2+
PFS (mo) CTFI >30d*4.65.3--

D, day; DCR, disease control rate; DOR, duration of response; FD, flat dose; mo, months; q3wk, every 3 weeks; CTFI, chemotherapy free interval.

Clinical trial identification

NCT01970540

Legal entity responsible for the study

PharmaMar SA

Funding

PharmaMar SA

Disclosure

M. Forster: Consulting or advisor or travel and accomodation in Lilly, Pfizer, BI, Novartis Merck, Astrazeneca. E. Calvo: Speakers\' Bureau in Novartis and travel or accomodation expenses in Lilly, PsiOxus, Novartis. M.P. Lopez Criado: Relation with Lilly, Bristol, roche, and travel, accomodations with Bristol. J.A. Lopez-Vilarino de Ramos, X.E. Luepke-Estefan: Employee in PharmaMar. C. Kahatt, P. Lardelli, A. Soto-Matos: Employee and Stock in PharmaMar. All other authors have declared no conflicts of interest.