Final results of a phase II study of oral vinorelbine (NVBo) monotherapy in patients (pts) with advanced EGFR-positive non-small-cell lung cancer (NSCLC) after failure of EGFR-TKI in first line (NAVoTRIAL 2)

Background

In advanced/metastatic EGFR-positive (EGFR+) NSCLC pts progressing after EGFR-TKIs failure in first line, single-agent chemotherapy (CT) may be offered in pts who are unfit for a platinum combination. In this study, NVBo was evaluated as monotherapy in advanced NSCLC EGFR+ pts who failed to EGFR-TKIs in first line.

Methods

Phase II, multicentre, open-label, international study. Main eligibility criteria: stage IIIB/IV NSCLC, EGFR + , prior EGFR-TKI treatment failure, Karnofsky PS ≥70, no prior CT or immunotherapy. Study treatment until progression or unacceptable toxicity: NVBo 60 mg/m² weekly for 3 weeks (first cycle), followed by 80 mg/m² weekly for subsequent cycles in absence of grade 3/4 toxicity. The primary endpoint was the disease control rate (DCR = CR + PR + SD, RECIST 1.1).

Results

30 pts included (March 2013 - November 2014). Main pts characteristics: median age: 66.8 years (60% ≥65 years); median Karnofsky PS 90%. Adenocarcinoma 96.7%. ≥3 organs involved (53.3%). All pts harboured EGFR mutation and received prior EGFR-TKI therapy: Gefitinib 73.3%, Erlotinib 16.7%, Afatinib 10%; 33.3% of pts had ≥2 comorbidities; Total number of cycles: 166 (443 doses administered); median number of cycles: 3.5 (range 1-20); median relative dose intensity: 77.6% (range 46.8-105); dose escalation was performed in 76.7 % of pts; Disease control rate 63.3% (95% CI [43.8-80]) and 23.3% of patients with stable disease ≥6 months. Median time to treatment failure: 2.7 months (range 0.4-13.6). Median PFS of 3.3 months (95% CI [1.6-5.4]) and OS of 13.1 months (95% CI [6.1-15.8]). Grade 3/4 toxicities per pt: neutropenia 53.3%, anemia 6.7%, leukopenia 26.7%, fatigue 16.7%, nausea 3.3% and vomiting 6.7%. Three cases of febrile neutropenia reported. No grade 3/4 diarrhoea, constipation, peripheral neuropathies or alopecia.

Conclusions

NVBo as single-agent CT is a well-tolerated option in advanced EGFR+ NSCLC pts beyond failure of EGFR-TKI in first line. Its favourable tolerability profile allows a prolonged disease control in non-progressing pts.

Clinical trial identification

EUDRACT Number 2012-003361-18 Sponsor's Protocol Code Number: PM0259CA229J1.

Legal entity responsible for the study

Institut de Recherche Pierre Fabre

Funding

Institut de Recherche Pierre Fabre

Disclosure

A. Camerini: Advisory board (Roche, Pierre-Fabre, Astra Zeneca). P. Landreau: Sponsor's (Pierre Fabre Laboratory) employee. J-C. Vedovato: Sponsor's employee (Pierre Fabre). All other authors have declared no conflicts of interest.