Nedaplatin Plus Docetaxel Extends OS In Advanced, Relapsed Squamous NSCLC

Using nedaplatin instead of cisplatin together with docetaxel significantly prolongs overall survival in Japanese patients with stage IIIB or IV or relapsed squamous non-small-cell lung cancer

medwireNews: Japanese researchers suggest that nedaplatin could be an alternative to cisplatin for first-line therapy of patients with advanced or relapsed squamous non-small-cell lung cancer (NSCLC).

Treatment with the platinum-derivative nedaplatin plus docetaxel resulted in significantly longer overall survival (OS) than cisplatin plus docetaxel, report Nobuyuki Yamamoto, from Wakayama Medical University, and colleagues in The Lancet Oncology.

But they highlight that their study was conducted solely in a Japanese population, which differs pharmacogenomically from Western populations in terms of responses and adverse events, and thus further confirmatory studies are warranted.

This point was also picked up by Yin Wu and James Spicer, from King’s College London in the UK, who write in a linked commentary: “The authors are right to conclude that nedaplatin can be thought of as a new treatment option for advanced or relapsed squamous non-small-cell lung cancer in the population that they studied, but more clinical data are needed before adoption of the drug as the new platinum standard worldwide.”

The phase III trial included 349 treatment-naive patients with advanced (stage IIIB or IV) or postoperative recurrent squamous NSCLC in the modified intention-to-treat analysis.

Median OS was 13.6 months for the 177 participants randomly assigned to receive open-label intravenous nedaplatin 100 mg/m2 and docetaxel 60 mg/m2. This was significantly longer than the 11.4 months recorded for the 172 patients treated with cisplatin 80 mg/m2 and docetaxel 60 mg/m2, with a hazard ratio of 0.81.

However, progression-free survival and response rates did not vary significantly between the treatment arms after a median follow-up of 39.3 months.

Nedaplatin-treated patients had a higher incidence of grade 3 or worse neutropenia, leukopenia and thrombocytopenia than those given cisplatin, at 82% versus 70%, 56% versus 44%, and 10% versus 0%, respectively.

But several “important” non-haematological side effects – such as fatigue (3 vs 12%), nausea (4 vs 14%) and anorexia (13 vs 26%) – were less frequent in the nedaplatin compared with the cisplatin group, say the study authors.

Yin Wu and James Spicer comment that the low incidence of nausea makes nedaplatin, a drug that was specifically developed to reduce toxicity, “an attractive alternative”.

But they think that “[i]n reality, the desired step change in the poor outcomes that most patients with advanced non-small-cell lung cancer still have is more likely to come from non-cytotoxic drugs.

“The spotlight now falls on further development of novel therapies directed at the various molecular targets already identified in this disease, and on immunotherapy.”

References

Shukuya T, Yamanaka T, Seto T, et al. Nedaplatin plus docetaxel versus cisplatin plus docetaxel for advanced or relapsed squamous cell carcinoma of the lung (WJOG5208L): a randomised, open-label, phase 3 trial. Lancet Oncol 2015; Advance online publication 27 October. doi: http://dx.doi.org/10.1016/S1470-2045(15)00305-8

Wu Y, SpicerJ. Nedaplatin: a new platinum for squamous lung cancer? Lancet Oncol 2015; Advance online publication 27 October. doi: http://dx.doi.org/10.1016/S1470-2045(15)00400-3

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