5734 - Phase II study of NAB-paclitaxel in SensiTivE and Refractory relapsed SCLC (NABSTER TRIAL)

Background

Despite high sensitivity to first-line chemotherapy (CT), most small-cell lung cancer (SCLC) patients relapse. Efficacy of 2nd-line CT is modest and influenced by treatment-free-interval (TFI). Topotecan demonstrated modest activity and significant haematological toxicity. Paclitaxel-based regimens showed to be active in this setting. Nab-paclitaxel, compared to paclitaxel, has a reduced incidence of hypersensitivity reactions and of neutropenia. Safety and efficacy in relapsed SCLC have not been prospectively studied.

Methods

This open-label phase II study enrolled patients with extensive- (ED) or limited-disease (LD) SCLC progressed during or after etoposide/platinum-based 1st-line CT with the aim to assess the activity and safety of Nab-paclitaxel. Patients were classified as refractory (TFI < 60 days) or sensitive (TFI ≥ 60 days). Eligible patients received Nab-paclitaxel 100 mg/mq on days 1,8,15 every 28 days for 6 cycles, progressive disease or intolerable toxicity. Computed tomography scan was performed every 2 cycles. Treatment could be continued beyond the 6^th cycle in presence of prolonged response, clinical benefit and good tolerance to drug. The primary endpoint was objective response, evaluated according to RECIST v1.1 criteria. The secondary endpoints were toxicity, measured according to NCI-CTCAE v4.03, progression-free and overall survival.

Results

From January 2017 to March 2018, 68 patients (25 refractory and 43 sensitive) were enrolled in the modified intentiontotreat population. Median age was 68.5 years (range 44-80). 44 patients were males and 57 had ED. Median follow-up was 5.8 months (IQR 3.37.1). Objective responses are currently being reviewed by an independent radiology panel. Most common toxicities (of all grades) were anemia (39%), leukopenia (27%), neutropenia (28%), nausea (19%), diarrhoea (21%), fatigue (52%), peripheral neuropathy (19%). The only severe toxicity (grade ≥3) was neutropenia (9%). In 13 patients treatment is still ongoing while 3/55 (5%) patients discontinued treatment for toxicity.

Conclusions

This is the first prospective study of Nab-paclitaxel for relapsed SCLC. Nab-paclitaxel demonstrated a manageable toxicity profile. Final activity data will be available for the meeting.

Clinical trial identification

EudraCT: 2016-000408-27; NCT03219762.

Legal entity responsible for the study

GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica).

Funding

Celgene.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.