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E.H. Tan
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OA23 - EGFR Targeted Therapies in Advanced NSCLC (ID 410)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:O.T. Brustugun, S. Lu
- Coordinates: 12/07/2016, 14:20 - 15:50, Stolz 2
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OA23.05 - First-Line Afatinib versus Gefitinib in EGFRm+ Advanced NSCLC: Updated Overall Survival Analysis of LUX-Lung 7 (ID 5347)
14:20 - 15:50 | Author(s): E.H. Tan
- Abstract
- Presentation
Background:
The irreversible ErbB family blocker afatinib and the reversible EGFR TKI gefitinib are approved for first-line treatment of advanced EGFRm+ NSCLC. This Phase IIb trial prospectively compared afatinib versus gefitinib in this setting.
Methods:
LUX-Lung 7 assessed afatinib (40 mg/day) versus gefitinib (250 mg/day) in treatment-naïve patients with stage IIIb/IV NSCLC harbouring a common EGFR mutation (Del19/L858R). Co-primary endpoints were PFS (independent review), time to treatment failure (TTF) and OS. Other endpoints included ORR and AEs. In case of grade ≥3/selected grade 2 drug-related AEs the afatinib dose could be reduced to 30 mg or 20 mg (minimum). The primary analysis of PFS/TTF was undertaken after ~250 PFS events. The primary OS analysis was planned after ~213 OS events and a follow-up period of ≥32 months.
Results:
319 patients were randomised (afatinib: 160; gefitinib: 159). At the time of primary analysis, PFS (HR [95% CI] 0.73 [0.57‒0.95], p=0.017), TTF (0.73 [0.58‒0.92], p=0.007) and ORR (70 vs 56%, p=0.008) were significantly improved with afatinib versus gefitinib. The most common grade ≥3 AEs were diarrhoea (13%) and rash/acne (9%) with afatinib and elevated ALT/AST (9%) with gefitinib. 42% of patients treated with afatinib had ≥1 dose reduction due to AEs; dose reductions were more common in females than males (77%/23%) and non-Asians than Asians (64%/36%). Dose reduction of afatinib did not negatively impact PFS (<40mg vs ≥40mg; HR [95% CI]: 1.34 [0.90‒2.00]) but reduced incidence and severity of drug-related grade ≥3 AEs. Treatment discontinuation due to drug-related AEs was the same in each arm (6%). The data cut-off for primary OS analysis occurred on 8 April 2016. At this time, median treatment duration (range) was 13.7 (0‒46.4) versus 11.5 (0.5‒48.7) months with afatinib and gefitinib. 25% (afatinib) and 13% (gefitinib) of patients received treatment for >24 months. 73% and 77% of patients in the afatinib and gefitinib arms had ≥1 subsequent systemic anti-cancer treatment, with 46% and 56% receiving a subsequent EGFR-TKI including osimertinib (14%)/olmutinib (14%). OS data, including subgroup analysis with respect to subsequent therapy will be presented at the meeting.
Conclusion:
Afatinib significantly improved PFS, TTF and ORR versus gefitinib in EGFRm+ NSCLC patients, with a manageable AE profile and few drug-related discontinuations. Dose adjustment of afatinib reduced drug-related AEs without compromising efficacy. Primary OS analysis will be reported.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-044 - Afatinib versus Gefitinib as First-Line Treatment for EGFR Mutation-Positive NSCLC Patients Aged ≥75 Years: Subgroup Analysis of LUX-Lung 7 (ID 5327)
14:30 - 15:45 | Author(s): E.H. Tan
- Abstract
Background:
The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of advanced EGFRm+ NSCLC. In the Phase IIb LUX-Lung 7 trial, afatinib significantly improved median progression-free survival (PFS; HR=0.73 [95% CI, 0.57–0.95], p=0.017), objective response rate (70% vs 56%, p=0.008) and time to treatment failure (TTF; HR=0.73 [95% CI, 0.58–0.92], p=0.007) versus gefitinib in this setting (Park et al. Lancet Oncol 2016). Here we evaluated the efficacy and safety of afatinib versus gefitinib in patients aged ≥75 years in a subgroup analysis of LUX-Lung 7 (NCT01466660).
Methods:
Treatment-naïve patients with stage IIIB/IV EGFRm+ NSCLC were randomized (1:1) to oral afatinib (40 mg/day) or gefitinib (250 mg/day), stratified by EGFR mutation type (Del19/L858R) and presence of brain metastases (Yes/No). Co-primary endpoints were PFS, TTF, and overall survival. Subgroup analyses of PFS and adverse events (AEs) by age (≥75/<75 years) were exploratory.
Results:
Of 319 patients randomised in LL7, 40 (13%) were aged ≥75 years (afatinib n=19, gefitinib n=21). Median PFS for both age groups was in line with the overall population and favoured afatinib versus gefitinib (patients ≥75 years: 14.7 vs 10.8 months, HR=0.69 [95% CI, 0.33–1.44]; patients <75 years: 11.0 vs 10.9 months, HR=0.76 [95% CI, 0.58–1.00]). The incidence of treatment-related AEs (grade 3/4) was slightly higher in the older subgroup (afatinib: 42%/0%; gefitinib: 24%/5%) than in the younger subgroup (afatinib: 28%/2%; gefitinib: 15%/<1%). There were no unexpected safety findings. The most common treatment-related AEs (all grade [grade 3]) with afatinib in the older patient subgroup were diarrhoea (89% [21%]), rash (63% [5%]), dry skin (37% [0%]), and decreased appetite (32% [0%]). Dose reduction/discontinuation of afatinib due to treatment-related AEs was required in 53%/16% and 40%/5% of the older and younger subgroup, respectively.
Conclusion:
A small subgroup of patients in the LUX-Lung 7 trial were ≥75 years old (13%). In exploratory subgroup analyses of patients aged ≥75 and <75 years old, advancing age did not adversely affect the PFS benefit and tolerability observed with afatinib versus gefitinib in treatment-naïve EGFRm+ NSCLC patients. These findings suggest that afatinib can provide an effective and tolerable treatment for older patients with EGFRm+ NSCLC.
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P3.02b-048 - Oral Vinorelbine Monotherapy in Patients with EGFR+ NSCLC after Failure of EGFR-TKI in First Line: A Prospective Study (ID 4315)
14:30 - 15:45 | Author(s): E.H. Tan
- Abstract
Background:
In advanced/metastatic EGFR+ NSCLC patients (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 (NAVoTRIAL 2), oral vinorelbine (NVBo) was evaluated as monotherapy in advanced NSCLC EGFR+ pts who failed to EGFR-TKIs in first line.
Methods:
Phase II, prospective, 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/m[2] weekly for 3 weeks (first cycle), followed by 80 mg/m[2] 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:
Final 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.
Conclusion:
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.
