Highlights
- •Prognosis of patients with advanced non–small-cell lung cancer (NSCLC) is poor.
- •Few options beyond platinum-based chemo and immunotherapy in non-squamous (ns) NSCLC.
- •Phase III trial of bevacizumab-paclitaxel (wPB) or docetaxel in 2nd/3rd line nsNSCLC.
- •wPB improved progression-free survival and objective response rate.
- •Safety profile was manageable and Quality of Life was preserved with wPB.
Abstract
Purpose
Second-line chemotherapy regimens have demonstrated poor benefit after failure of
platinum-based chemotherapy in advanced non-squamous non–small-cell lung cancer (nsNSCLC).
Methods
In this multicentre, open-label phase III trial, patients with advanced nsNSCLC treated
with one or two prior lines, including one platinum-based doublet, were centrally
randomised to receive 90 mg/m2 of paclitaxel (D1, D8, D15) plus 10 mg/kg of bevacizumab (D1, D15) every 28 days
or docetaxel (75 mg/m2) every 21 days; crossover was allowed after disease progression. Primary end-point
was progression-free survival (PFS). ClinicalTrials.gov registration number: NCT01763671.
Results
One hundred sixty six patients were randomised (paclitaxel plus bevacizumab: 111,
docetaxel: 55). The median PFS was longer in patients receiving paclitaxel plus bevacizumab
than in patients receveing docetaxel [5·4 months versus 3·9 months, adjusted hazard
ratio (HR) 0·61 (95% confidence interval [CI]: 0·44–0·86); p = 0·005]. Objective response
rates (ORRs) were 22·5% (95% CI: 14·8–30·3) and 5·5% (95% CI: 0·0–11·5) (p = 0·006),
respectively. Median overall survivals were similar (adjusted HR 1·17; p = 0·50).
Crossover occurred in 21 of 55 (38·2%) docetaxel-treated patients. Grade III-IV adverse
events (AEs) were reported in 45·9% and 54·5% of patients treated with paclitaxel
and bevacizumab or docetaxel, respectively (p = NS), including neutropenia (19·3%
versus 45·4%), neuropathy (8·3% versus 0·0%) and hypertension (7·3% versus 0·0%).
Three patients died due to treatment-related AEs (1·8% in each group).
Conclusion
Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared
with docetaxel in patients with nsNSCLC, with an acceptable safety profile. These
results place weekly paclitaxel plus bevacizumab as a valid option in this population.
Clinical trials registration number
ClinicalTrials.gov Identifier: NCT01763671.
Keywords
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References
- Nivolumab versus docetaxel in advanced nonsquamousnon-small-cell lung cancer.N Engl J Med. 2015; 373: 1627-1639https://doi.org/10.1056/NEJMoa1507643
- Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial.Lancet. 2016; 387: 1540-1550https://doi.org/10.1016/S0140-6736(15)01281-7
- Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentrerandomised controlled trial.Lancet. 2017; 389: 255-265https://doi.org/10.1016/S0140-6736(16)32517-X
- Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer.N Engl J Med. 2018; 378: 2078-2092https://doi.org/10.1056/NEJMoa1801005
- Atezolizumab for first-line treatment of metastatic nonsquamousNSCLC.N Engl J Med. 2018; 378: 2288-2301https://doi.org/10.1056/NEJMoa1716948
- Treatment paradigms for patients with metastatic non-small-cell lung cancer: first-, second-, and third-line.CurrOncol. 2012; 19: S52-S58
- Non-small cell lung cancer.J Natl Compr Canc Netw. 2012; 10: 1236-1271
- Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2012; Suppl7: vii56-vii64
- Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial.Lancet. 2014; 384: 665-673https://doi.org/10.1016/S0140-6736(14)60845-X
- Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial.Lancet Oncol. 2014; 15: 143-155https://doi.org/10.1016/S1470-2045(13)70586-2
- Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.N Engl J Med. 2006; 355: 2542-2550
- Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer.N Engl J Med. 2007; 357: 2666-2676
- Phase III study of bevacizumabplus docetaxelcompared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2–negative metastatic breast cancer.J ClinOncol. 2010; 28: 3239-3247
- RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2–negative, locally recurrent or metastatic breast cancer.J ClinOncol. 2011; 29: 1252-1260
- Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients.Bull Cancer. 2013; 100: 30-37https://doi.org/10.1684/bdc.2013.1864
- Bevacizumab and weekly paclitaxel for non-squamous non-small cell lung cancer patients: a retrospective study.Lung Canc. 2013; 80: 197-202https://doi.org/10.1016/j.lungcan.2013.01.015
- BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy.Canc Res. 2008; 68: 4774-4782
- Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2.J ClinOncol. 2010; 28: 780-787
- Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2018 Oct 1; 29: iv192-iv237
- Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial.Lancet. 2011; 378: 1079-1088
- The blockade of immune checkpoints in cancer immunotherapy.Nat Rev Canc. 2012; 12: 252-264
- First-line treatment of NSCLC with bevacizumab: real world data from an Italian regional based survey.t al.J Chemother. 2017; 29: 38-41https://doi.org/10.1080/1120009X.2016.1219498
- Atezolizumab for first-line treatment of metastatic nonsquamousNSCLC.N Engl J Med. 2018 Jun 14; 378: 2288-2301
- Efficacy of weekly paclitaxel-bevacizumab combination in advanced nonsquamous non-small cell lung cancer (NSCLC) : a retrospective multicentric study.Ann Oncol. 2019; 30: v602-v660
- Ann Oncol. 2019; 30: xi16-xi32https://doi.org/10.1093/annonc/mdz449
Article info
Publication history
Published online: April 07, 2020
Accepted:
February 22,
2020
Received:
February 20,
2020
Identification
Copyright
© 2020 Elsevier Ltd. All rights reserved.
