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  • br Results br Discussion The Intergroupe Francophone de Canc

    2019-08-26


    Results
    Discussion The Intergroupe Francophone de Cancerologie Thoracique reported QOL analysis of the 0501 trial testing the combination carboplatin/paclitaxel versus single agent gemcitabine or vinorelbine, using the EORTC QLQ-C30 [14]. No significant QOL deterioration was seen with carboplatin/paclitaxel; even, a statistically significant advantage was found in time until definitive deterioration (TUDD) of physical functioning and nausea/vomiting using a 5-point threshold as minimum clinically important difference (MCID), and of fatigue and nausea/vomiting using a 10-point MCID. The analysis was not adjusted for competitive risks and the findings related to nausea/vomiting are counterintuitive given the expected toxicity profile of the drugs. However, interpretation was clearly affected by the positive result of the overall survival analysis, allowing the Authors to define as positive the fact that no QOL worsening was evident and, eventually, some advantage was found. The context is different for MILES-3 and MILES-4, because cisplatin addition does not prolong survival and lack of worsening cannot be considered enough for a positive interpretation of the QOL data. Moreover, we found some worsening with cisplatin in items (sore A 61603 and alopecia) investigated through the lung cancer specific LC13 questionnaire, which was not used in the 0501 trial. As a technical point, we believe that the possible impact of the threshold value for MCID should be clarified. Actually, both the 5-point and 10-point thresholds are supported by previous literature [11,15]. Consistently with our strategy in previous NSCLC trials, we planned to use the 10-point threshold that is more challenging in terms of hope for QOL improvement, a goal that should be pursued with a potentially toxic treatment like platinum-containing chemotherapy [2,4,16,17]. The larger threshold, therefore, is more demanding for the experimental arm in analytic frames looking for improvement (ie the best response analysis), while turns to be conservative in favour of the experimental arm in time-to-deterioration analysis; nevertheless, we actually found a significantly shorter TTD for sore mouth and hair loss with the addition of cisplatin, consistent with the expected toxicity profile of the treatment.
    Conclusions
    Funding MILES-3 trial was partially supported by the Italian Drug Agency (AIFA grant ARM8KAJZK). Eli Lilly provided the pemetrexed, free of charge, and partial funding for MILES-4 study. Neither AIFA nor Eli Lilly played any role in study design, collection, analysis and interpretation of data, writing of the report and the decision to submit the article for publication.
    Conflicts of interest A.Morabito – Speakers’ Bureau: Genentech, Eli Lilly, Pfizer, Boehringer Ingelheim, AstraZeneca, MSD Oncology; M.C. Piccirillo - Honoraria: Merck Sharp & Dohme and Astra Zeneca. Travel, Accommodations, Expenses: Bayer, Roche, Astra Zeneca; P.Maione – None; A.Luciani – None; L.Cavanna – Consulting or Advisory Role: AstraZeneca, Merck; L.Bonanno – None; V.Filipazzi – None; S.Leo – None; S.Cinieri - Speakers’ Bureau: Eli Lilly; F.Morgillo – None; M.A.Burgio – None; D.Ferrara – None; F.Rosetti – Travel, Accommodations, Expenses: Bristol-Myers Squibb; R.Bianco – None; F.Artioli – None; D.Cortinovis – None; V.Gebbia – None; V.Fregoni – None; M.Mencoboni – Consulting or Advisory Role: Merck Sharp & Dohme. Travel, Accommodations, Expenses: Roche, Ipsen, Bristol-Myers Squibb; C.Sandomenico – None; A.Rossi – None; A.Montanino – None; A.Manzo – None; G.Rocco – None; L.Arenare – None; G.Daniele – Honoraria: Bayer Schering Pharma; S.Signoriello – None; C.Gallo – None; F.Perrone – Honoraria: Bayer AG, Daiichi Sankyo, Ipsen, AstraZeneca, Bristol-Myers Squibb. Research Funding: Roche (Inst), Bayer AG (Inst). Travel, A 61603 Accommodations, Expenses: Bayer AG, Daiichi Sankyo; C.Gridelli – Consulting or Advisory Role: Bristol-Myers Squibb, MSD Oncology. Speakers’ Bureau: Genentech, MSD Oncology, Bristol-Myers Squibb. Research Funding: Eli Lilly.