J-AXEL: nab-paclitaxel at least equal to docetaxel in pretreated NSCLC

Various advantages have been described for nab-paclitaxel, the albumin-bound, solvent-free, nanoparticle formulation of paclitaxel [1-3]. Phase II data showed favorable results in patients with pretreated advanced NSCLC who obtained an ORR of 32 % and median PFS of 5 months [4]. Therefore, the randomized, phase III study reported by Nakamura et al. compared nab-paclitaxel 100 mg/m² on days 1, 8 and 15 three-weekly with docetaxel 60 mg/m² every three weeks in patients with stage IIIB/IV or recurrent NSCLC previously treated with cytotoxic chemotherapy [5]. The analysis aimed to demonstrate non-inferiority of nab-paclitaxel with respect to OS. Both arms included approximately 250 patients.

Significant PFS and ORR benefits

Non-inferiority of nab-paclitaxel in terms of OS was confirmed with the protocol-specified margin of 1.25 in the intent-to-treat population (HR, 0.85; 95.2 % CI, 0.68–1.070). Median OS amounted to 16.2 and 13.6 months with nab-paclitaxel and docetaxel, respectively. As specified by the protocol, superiority of nab-paclitaxel over docetaxel for OS was tested after non-inferiority had been shown. However, nab-paclitaxel did not significantly improve survival, although this was the case for both PFS and ORR. Median PFS was 4.2 vs. 3.4 months with nab-paclitaxel and docetaxel (HR, 0.76; p = 0.0042). In the total group (n = 459), 29.9 % vs. 15.4 % of patients responded to treatment (p = 0.0002; Figure). For the patients with squamous histology (n = 94), this was 30.4 % vs. 10.4 % (p = 0.0207), and for those with non-squamous NSCLC (n = 365), 29.7 % vs. 16.7 % (p = 0.0042). The results for both PFS and OS favored nab-paclitaxel across various subgroups pertaining to age, sex, ECOG performance status, histology, smoking status, disease stage, EGFR mutation status, and pretreatment.

Hematologic toxicity with docetaxel and neuropathy with nab-paclitaxel

Among AEs, leukopenia and neutropenia occurred significantly more often with docetaxel than with nab-paclitaxel (p < 0.0001 for both comparisons); correspondingly, docetaxel conferred a significantly higher incidence of febrile neutropenia (22.1 % vs 2.0 %). On the other hand, peripheral ­sensory neuropathy was more frequent with nab-paclitaxel (55.5 % vs. 20.1 %, p < 0.0001). The authors stressed in their summary that nab-paclitaxel should be considered a standard option for previously treated patients with advanced NSCLC.

Figure: Objective responses rates achieved with nab-paclitaxel vs. docetaxel in the ITT population and according to histology

REFERENCES

1. Desai N et al., Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res 2006; 12(4): 1317-1324
2. Sasaki Y et al., Phase II trial of nanoparticle albumin-bound paclitaxel as second-line chemotherapy for unresectable or recurrent gastric cancer. Cancer Sci 2014; 105(7): 812-817
3. Gradishar WJ et al., Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol 2009; 27(22): 3611-3619
4. Sakata S et al., Phase II trial of weekly nab-paclitaxel for previously treated advanced non-small cell lung cancer: Kumamoto thoracic oncology study group (KTOSG) trial 1301. Lung Cancer 2016; 99: 41-45
5. Nakamura A et al., Phase III study comparing nab-paclitaxel with docetaxel in patients with previously treated advanced non-small cell lung cancer_J-AXEL. WCLC 2020, OA03.05

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