Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)

Francesco Gelsomino, Marcello Tiseo, Fausto Barbieri, Ferdinando Riccardi, Luigi Cavanna, Antonio Frassoldati, Angelo Delmonte, Lucia Longo, Claudio Dazzi, Saverio Cinieri, Ida Colantonio, Francesca Sperandi, Giuseppe Lamberti, Stefano Brocchi, Lorenzo Tofani, Luca Boni, Andrea Ardizzoni, Francesco Gelsomino, Marcello Tiseo, Fausto Barbieri, Ferdinando Riccardi, Luigi Cavanna, Antonio Frassoldati, Angelo Delmonte, Lucia Longo, Claudio Dazzi, Saverio Cinieri, Ida Colantonio, Francesca Sperandi, Giuseppe Lamberti, Stefano Brocchi, Lorenzo Tofani, Luca Boni, Andrea Ardizzoni

Abstract

Background: Despite sensitivity to first-line chemotherapy, most small-cell lung cancer (SCLC) patients relapse. In this setting, topotecan demonstrated modest activity with significant toxicity. Paclitaxel was also active. This study was designed to evaluate activity and safety of nab-paclitaxel in relapsed SCLC.

Methods: In this multicentre prospective Phase 2 trial, patients with refractory or sensitive SCLC progressed to first-line platinum-based chemotherapy received nab-paclitaxel 100 mg/smq on days 1, 8, 15 every 4 weeks up to six cycles, progressive disease or intolerable toxicity. Primary endpoint was investigator-assessed objective tumour response. Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).

Results: Of the 68 patients treated, partial response was 8% in the refractory cohort and 14% in the sensitive cohort. Most common toxicities of any grade were fatigue (54%), anaemia (38%), neutropenia (29%), leukopenia (26%) and diarrhoea (21%). Median PFS was similar in both refractory (1.8 months) and sensitive cohorts (1.9 months), while median OS was longer in sensitive one (6.6 versus 3.6 months).

Conclusions: Although nab-paclitaxel has shown some modest anti-tumour activity in relapsed SCLC, associated with a favourable toxicity profile, the primary end-point of the study was not met.

Clinical trial registration: Clinical Trial registration number is ClinicalTrials.gov Identifier: NCT03219762.

Conflict of interest statement

A.A. has received research grant support from BMS and Celgene; personal fees for serving in a consultant and/or advisory role for BMS, MSD and Boehringer; honoraria from Eli-Lilly and Pfizer. A.F. has received personal fees for serving in a consultant and/or advisory role for Novartis, Roche and Astrazeneca; honoraria from Novartis, Astrazeneca, Pfizer, Lilly, Eisai, Roche, Novartis and Celgene. L.C. has received personal fees for serving in a consultant and/or advisory role for Astrazeneca and Merck; honoraria from Celgene, Pfizer and Ipsen. The remaining authors declare no competing interests.

Figures

Fig. 1. CONSORT flow diagram.
Fig. 1. CONSORT flow diagram.
It displays the progress of all participants through the NABSTER trial.
Fig. 2. Waterfall plot.
Fig. 2. Waterfall plot.
It describes the changes in tumor size in all evaluable participants with target lesions. Blue bars represent sensitive patients, while orange bars are refractory ones. The black/white signal at the top of each bar corresponds to central radiological review for each individual patient.
Fig. 3. PFS and OS in modified…
Fig. 3. PFS and OS in modified ITT population.
Probabilities of PFS (a) and OS (b) were calculated according to the Kaplan–Meier product-limit method. In both graphs (a and b), continuous and dashed curves represent survival probabilities in refractory and sensitive cohorts, respectively.

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