Abstract 1784P
Background
Remarkable activity was observed with lurbinectedin in patients (pts) with relapsed small-cell lung cancer (SCLC) in a phase II Basket trial (Trigo et al. 2020). NCCN guidelines recommend platinum re-challenge if chemotherapy-free interval (CTFI) >180 days (d) based on small clinical trials mostly conducted in the 1980s. Recent data on re-challenge with CTFI >90 d showed overall response rate (ORR) of 45-49% and median overall survival (OS) of 7.5-7.9 months (mo) (Genestreti et al. 2015; Monnet et al. 2019).
Methods
In the SCLC cohort of the Basket trial, 60 pts with CTFI >90 d (20 pts with CTFI >180 d) pretreated with one prior platinum-based line were treated with lurbinectedin 3.2 mg/m2 1-hour i.v. infusion q3wk.
Results
Median (range) age was 59 (44-78) years; 56.7% were males; ECOG PS 0/1/2 was 45/50/5%; 31.7% had liver metastases; 58% extensive disease at diagnosis; all received prior platinum; 8.3% received prior immunotherapy; and best response to prior platinum-based chemotherapy was CR (13.3%), PR (71.7%), and SD (13.3%). Median (range) CTFI was 4.7 mo (2.9-16.1) mo. Median (range) number of lurbinectedin cycles was 6 (1-24). Table: 1784P
| CTFI >90 d (n=60) | CTFI >180 d (n=20) | |||
| IA | IRC | IA | IRC | |
| ORR (95% CI), % (confirmed responses) | 45.0 (32.1-58.4) | 43.3 (30.6-56.8) | 60.0 (36.1-86.9) | 50.0 (27.2-72.8) |
| Disease Control Rate at 8 wks, % | 81.7 (69.6-90.5) | 73.3 (60.3-83.9) | 95.0 (75.1-99.9) | 80.0 (56.3-94.3) |
| Median Duration of Response (95% CI), mo | 6.2 (3.5-7.3) | 5.3 (4.9-7.0) | 5.5 (2.9-11.2) | 5.5 (2.8-8.5) |
| Median OS (95% CI), mo | 11.9 (9.7-16.2) | 16.2 (9.6-NR) | ||
| OS at 12 mo (95% CI), % | 48.3 (32.5-64.1) | 60.9 (35.7-86.2) | ||
| OS at 24 mo (95% CI), % | 21.0 (8.2-33.8) | 27.1 (5.4-48.8) |
CI: confidence interval; d: days; IA: Investigator's assessment; IRC: Independent Review Committee; NR: not reached; wks: weeks.
Main adverse events were hematological (grade 3/4 neutropenia: 25%; febrile neutropenia, 1.7%; grade 3/4 anemia: 10%) and grade 3 fatigue (10%). Further treatment after lurbinectedin was mainly platinum-based chemotherapy (55%) and immunotherapy (20.5%).
Conclusions
Lurbinectedin is effective and well-tolerated in platinum-sensitive relapsed SCLC, especially when CTFI >180 d. Lurbinectedin is an alternative to platinum re-challenge.
Clinical trial identification
NCT02454972.
Editorial acknowledgement
Legal entity responsible for the study
PharmaMar.
Funding
Has not received any funding.
Disclosure
V. Subbiah: Research grant/Funding (self): PharmaMar, Loxo Oncology, Novartis, Bayer, GlaxoSmithKline, Nanocarrier, Vegenics, Celgene, Northwest Biotherapeutics, Berghealth, Incyte, Fujifilm, D3, Pfizer, Multivir, Amgen, AbbVie, Alfa-sigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelix; Travel/Accommodation/Expenses: Novartis, PharmaMar, Astra Zeneca/MedImmune, Apollo Hospitals, Sathgen Biotech, ASCO, ESMO. L. Paz-Ares: Honoraria (self), Leadership role, Research grant/Funding (self), Travel/Accommodation/Expenses: Genomica, Roche, Astra Zeneca, MSD, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bochringer Ingelheim, PharmaMar, Celgene, Sysmex, Incyte. B. Besse: Research grant/Funding (self): To institution: Sponsored Research at Gustave Roussy Cancer Center AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Ignyta, IPSEN, Inivata, Janssen, Merck K. V. Moreno: Advisory/Consultancy: BMS, Janssen. K. Zaman: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astra Zeneca, Celgene, Lilly, Pfizer,Eisai, Novartis, Lilly,. J.A. Lopez-Vilarino: Honoraria (self), Shareholder/Stockholder/Stock options: PharmaMar. C.M. Fernandez: Honoraria (self): PharmaMar. C. Kahatt, M. Siguero, A. Zeaiter: Honoraria (self), Shareholder/Stockholder/Stock options: PharmaMar. R. Lopez Lopez: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Lilly, Novartis, Merck, Roche, BMS, Pfizer, PharmaMar, Bayer, Pierre Fabre. S. Ponce Aix: Speaker Bureau/Expert testimony: Roche, BMS, MSD, Lilly, AstraZeneca. V. Boni: Speaker Bureau/Expert testimony: START Madrid CIOCC, Ideaya, Solti. J.M. Trigo Perez: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS, MSD, Takeda, Eisai, Astra Zeneca, Bayer. All other authors have declared no conflicts of interest.