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InOncology.com

RealGiDo: A Real-World Study of Afatinib Dose Adjustment in patients with EGFR mutation-positive advanced NSCLC

Afatinib Dose Adjustment in Clinical Practice

A global, multicentre medical chart review of first-line afatinib* dose adjustment in real-world clinical practice in patients with advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).

Trial CT.gov-Identifier: NCT027518791

Watch the video below to find out more about the study design and outcomes of the RealGiDo study.

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Patients

  • Advanced, EGFR mutation-positive, tyrosine kinase inhibitor-naïve NSCLC
  • Common EGFR mutations (del19, L858R)
  • Treatment with afatinib according to the approved label
  • Patients who started treatment ≥6 months before enrolment

 

N=228

Analysis included patients treated with a reduced starting dose of afatinib (≤30 mg), those with a dose reduction (<40 mg) and those with no dose reduction (≥40 mg)

Outcome measures

Primary outcome measures:

  • Percentage of patients with adverse drug reactions (ADRs) by severity
  • Time to treatment failure (TTF; synonymous to time on treatment)
  • Time to progression (TTP)

 

Secondary outcome measure:

  • Percentage of patients receiving a modified starting dose, and reasons for modifying the starting dose

Results

Patients and Treatment

Baseline characteristics of patients in RealGiDo2 were generally consistent with the global, Phase III LUX-Lung 3 trial.3 However, in RealGiDo, there were more patients with EGFR Del19 mutations (78% vs 49%) and fewer Asian patients (44% vs 72%); furthermore, RealGiDo included patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 2–3 (12% of patients).2,3

Thirty-one percent of patients received a modified afatinib starting dose of <40 mg/day and the reasons for modifying the starting dose were broad but most commonly related to patient characteristics.2

Afatinib starting dose2

image

Reasons for modifying starting dose2

RealGiDo study: reasons for modified starting dose

Overall, 177 (78%) of patients in RealGiDo had a dose modification.2,4 Of these, 149 had dose reductions only, and 24 had both dose reductions and escalations.Among patients who received afatinib 40 mg/day as their starting dose, 86% of dose reductions occurred with the first 6 months of treatment and the rate of dose reductions was numerically higher in RealGiDo than LUX-Lung 3 (67% vs 53%).2,4

Safety

The overall safety profile of afatinib was similar in the overall population and in the group of patients who started with afatinib 40 mg/day.2 All-grade ADRs and Grade ≥3 ADRs occurred in 94% and 25% of the overall RealGiDo population, respectively.2 Among patients who received a starting dose of afatinib 40 mg/day (n = 155), 94% had an ADR, 28% had a Grade ≥3 ADR and 5% had a serious AE.2 There were fewer Grade ≥3 ADRs (28% vs 49%) and serious AEs (5% vs 14%) in patients treated with afatinib 40 mg/day in RealGiDo than in the LUX-Lung 3 trial.2,3

The most common ADRs in the overall population in RealGiDo were diarrhoea, rash/acne, paronychia/nail effect and stomatitis/mucositis.2 The incidences of these ADRs were lower in RealGiDo than in LUX-Lung 3 (diarrhoea, 75% vs 95%; rash/acne, 63% vs 89%; paronychia/nail effect, 49% vs 57%; stomatitis/mucositis, 34% vs 72%).2,3 Overall, no new safety signals were identified in RealGiDo.

Among the 91 patients who had a dose reduction within the first 6 months after starting on afatinib 40 mg/day, 99% experienced an ADR of any grade prior to dose modification, compared with 71% after dose modification.2 The severity of ADRs was reduced following dose modification; the incidences of Grade 1, 2, 3 and 4 ADRs before and after dose modification were 11.0% and 20.6%, 57.5% and 37.0%, 27.4% and 12.3%, and 2.7% and 1.4%, respectively.2Dose reductions led to decreases in the incidence and severity of ADRs, including the most commonly reported.2

Among 71 patients who started on ≤30 mg/day afatinib, 95.8% had an ADR of any grade, 16.9% had a Grade 3 ADR and there were no Grade 4 ADRs.2

Overall safety profile before and after dose reduction in patients who had a dose reduction within the first 6 months after starting on afatinib 40 mg/day2

RealGiDo study: Overall safety profile before and after dose reduction

Common ADRs before and after dose reduction in patients who had a dose reduction within the first 6 months after starting on afatinib 40 mg/day2

RealGiDo study: Common ADRs before and after dose reduction

Overall safety profile by starting dose2

RealGiDo study: ADRs by starting dose

Effectiveness

TTF 

Median TTF was 18.7 months (95% confidence interval [CI]: 15.1–21.5) in the overall population, 19.5 months (95% CI: 13.4–not evaluable [NE]) in patients who remained on an afatinib dose of ≥40 mg/day for the first 6 months (n=66), 17.7 months (95% CI: 14.5–21.5) in patients who had a dose reduction to <40 mg/day within the first 6 months (n=91), and 19.4 months (95% CI: 12.9–NE) in patients who started with afatinib ≤30 mg/day (n=71; p=0.543).2

The proportion of patients remaining on treatment at 12 months was estimated as 70% in the patients who remained on ≥40 mg/day for the first 6 months, 74% in patients who had a dose reduction to <40 mg/day within the first 6 months and 66% in patients who started with afatinib ≤30 mg/day.2 The corresponding rates at 18 months were 53%, 50% and 53%, respectively.2

TTF among patients in RealGiDo by dose received2

RealGiDo study: TTF by dose received

CI, confidence interval; NR, no response.

TTP

Median TTP was 20.8 months (95% CI: 19.1–25.9) in the overall population, 29.0 months (95% CI: 17.9–NE) in patients who remained on an afatinib dose of ≥40 mg/day, 20.0 months (95% CI 14.7–23.0) in patients who had a dose reduction to <40 mg/day within the first 6 months and 25.9 months (95% CI: 17.3–NE) in patients who started with afatinib  ≤30 mg/day (p=0.392).2

The proportion of patients without progressive disease or tumour-related death at 12 months was estimated as 79% in patients who remained on afatinib ≥40 mg/day for the first 6 months, 84% in patients who had a dose reduction to <40 mg/day within the first 6 months and 86% in patients who started with afatinib ≤30 mg/day.2 The corresponding rates at 18 months were 65%, 60% and 64%, respectively.2

TTP among patients in RealGiDo by dose received2

RealGiDo study: TTP by dose received

CI, confidence interval; NR, no response.

Conclusion

Tolerability-guided afatinib dose adjustment in real-world clinical practice reduced the frequency and intensity of ADRs, without impacting effectiveness.2 As seen in the LUX-Lung trials,4,5 the effectiveness of afatinib was consistent regardless of whether patients had a dose reduction or a modified starting dose.2 Overall, these results show that outcomes can be optimised by tailoring afatinib dose based on individual patient characteristics and ADRs.

References

1

Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT02751879 (Accessed: May 2018).

2

Halmos B, et al. Lung Cancer 2018. doi: https://doi.org/10.1016/j.lungcan.2018.10.028 [Epub ahead of print].

3

Sequist LV, et al. J Clin Oncol 2013;31(27):3327–34.

4

Yang JC, et al. Ann Oncol 2016;27(11):2103–10

5

Hirsch V, et al. Poster presented at ASCO 2016 (Poster 369).

*Afatinib is approved in more than 80 markets including the EU, Japan, Taiwan, and Canada under the brand name GIOTRIF®, in the US under the brand name GILOTRIF® and in India under the brand name Xovoltib®; for the full list please see here. Registration conditions differ internationally; please refer to locally approved prescribing information.

 

© 2018 Boehringer Ingelheim International GmbH. All rights reserved.

 

Last updated: October 2018