ELCC 2014 News: Cabazitaxel Fails to Meet the Primary Endpoint in a Randomised Phase II Study in SCLC Patients

The study compared cabazitaxel vs. topotecan in patients who progressed during or after first-line platinum-based chemotherapy

Cabazitaxel failed to meet a primary endpoint of showing superior progression-free survival (PFS) and additionally showed less favourable median overall survival (OS) compared to topotecan in an international, randomised open-label phase II trial performed in patients with small-cell lung cancer (SCLC), who had progressed during or after first-line platinum-based chemotherapy. The results were presented by Dr Tracey Evans of the Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, USA in a proffered papers session at the 4th European Lung Cancer Conference (26-29 March 2014, Geneva, Switzerland).

Platinum-based chemotherapy is the first-line treatment and standard of care for SCLC, but despite high response rates, most patients with SCLC experience rapid relapse and die from systemic metastases. Therefore, more effective second-line treatments are needed. Taxanes are active as second-line therapy in SCLC. Cabazitaxel, a semi-synthetic derivative of a natural taxoid, shows to be effective in second-line treatment for other solid tumours.

A need for more effective second-line treatments in SCLC

The authors compared cabazitaxel vs. topotecan in the randomised open-label phase II trial in patients with locally advanced or metastatic SCLC who had progressed during or after first-line platinum-based chemotherapy. Patients with ECOG PS ≤1, ≤1 prior chemotherapy and no prior taxane and topotecan treatment were enrolled. Patients were split into chemo-sensitive and chemo-refractory subgroups and stratified by presence or not of brain metastases and level of lactate dehydrogenase (LDH).

Endpoints included progression-free survival (PFS) as a primary endpoint, overall survival (OS), safety and health-related quality of life.


The primary point of progression-free survival improvement versus topotecan was not met in phase II study in SCLC patients who progressed during or after first-line platinum-based chemotherapy.
© Tracey Evans

In total, 179 patients were randomised, 90 to cabazitaxel and 89 to topotecan arm. Median age was 61 years. Baseline characteristics were balanced between treatment arms with approximately 50% of chemo-refractory patients in each arm. Median number of cycles received was 2 in cabazitaxel arm and 4 in topotecan arm.

Median PFS was 1.4 months in cabazitaxel arm and 3.0 months in topotecan arm. The primary endpoint of improvement in PFS for cabazitaxel vs. topotecan was not met. Similar results were observed in the chemo-sensitive and chemo-refractory subgroups. Cabazitaxel was less favourable than topotecan for median OS (5.2 months in cabazitaxel vs. 6.8 months in topotecan arm).

All-grade adverse events were more frequent with topotecan (94.3%) vs. cabazitaxel (88.8%), as were grade 3/4 adverse events (71.6% in topotecan and 58.4% in cabazitaxel arm). However, febrile neutropenia, neutropenic infection and neutropenic sepsis were similar across both arms. Growth factors were not prophylactically used in the study. No new safety concerns were identified for cabazitaxel.

The authors concluded that cabazitaxel failed to show superior PFS over topotecan. In addition, it showed a less favourable median OS rate in comparison to topotecan in patients with SCLC who had progressed during or after first-line chemotherapy.

Dr Pilar Garrido, who discussed the study results, said that the strong signal of cabazitaxel activity in SCLC was not actually seen in phase I studies. She said that SCLC is a genetically complex cancer, but the oncology community should focus on identifying the underlying mechanism for rapid development of resistance to find more effective treatments for SCLC patients.


Abstract 67O: Cabazitaxel (cbz) vs topotecan (tpt) in patients (pts) with small cell lung cancer (SCLC) with progressive disease during/after first-line (1L) treatment with platinum-based chemotherapy (ctx).

Dr Evans reported that he receives honoraria or consultation fees from Lilly and Genentech. Her husband is on the speakers bureau for Genentech. Dr Cho, who is a study co-author, receives grants/research support from Novartis, and honoraria or consultation fees from Novartis, AstraZeneca and GSK. Dr Chadjaa is a stock shareholder and a Sanofi employee. All other authors declared no conflicts of interest.

The European Lung Cancer Conference (ELCC) is organised by the European Society for Medical Oncology (ESMO) and the International Association for the Study of Lung Cancer (IASLC). During the four-day programme, attendees benefit from educational and scientific updates provided by thoracic oncology specialists on different multidisciplinary topics important for research and clinical practice in the field of lung cancer.