Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial

Abstract

In this prospective phase III trial, afatinib combined with paclitaxel improved progression-free survival and objective response, compared with single-agent chemotherapy, in patients with NSCLC who were clinically enriched for ErbB dependency having failed platinum-based chemotherapy, gefitinib/erlotinib and afatinib monotherapy after initial benefit on each tyrosine kinase inhibitor.

Update on afatinib-based combination regimens for the treatment of EGFR mutation-positive non-small-cell lung cancer

“…The expansion part of the study is currently recruiting patients with NSCLC harboring sensitive EGFR mutations and acquired resistance to afatinib, in the absence of T790M mutation [14]. afatinib plus paclitaxel A recent randomized Phase III study, LUXLung 5 (NCT01085136), assessed the efficacy and tolerability of paclitaxel added to afatinib in heavily pretreated NSCLC patients who had progressed following ≥1 line of chemotherapy, and whose tumors had progressed following initial disease control (≥12 weeks) on erlotinib or gefitinib and subsequently on afatinib monotherapy [15]. Compared with single-agent chemotherapy alone, paclitaxel plus afatinib significantly improved PFS (median 5.6 vs 2.8 months; p = 0.003) and ORR (32.1 vs 13.2%; p = 0.005) in this late-line treatment setting, while treatment-related adverse events were consistent with those previously reported for each agent.…”

“…The investigators concluded that LUX-Lung 5 was the first prospective study to support the concept of maintaining ErbB targeting beyond formal disease progression in oncogene-addicted NSCLC, and added that the combination of afatinib plus paclitaxel warrants consideration in patients with EGFR T790M mutation-negative NSCLC who have progressed on a first-generation EGFR-TKI [15]. In contrast to LUX-Lung 5, recent studies have demonstrated that continued exposure to erlotinib plus chemotherapy [24] or gefitinib plus chemotherapy [25] in heavily pretreated patients progressing after first-line therapy with an EGFR-TKI did not confer any additional clinical benefit, and increased toxicity versus chemotherapy alone.…”

“…Here, recent developments with afatinib-based combinations that may have particular promise in the areas of unmet need described above are discussed. Such regimens include combinations with EGFR monoclonal antibodies, such as cetuximab and nimotuzumab [12,13], IGFsignaling inhibitors, such as xentuzumab [14], chemotherapeutic agents including paclitaxel [15] and immune checkpoint inhibitors.…”

The First Clinical Experience With Afatinib in Russian Federation

“…и 2,8 мес., ОР 0,60, 95% ДИ 0,43-0,85, р = 0,003). Тенденция преимущества афатиниба наблюдалась и в отношении ЧОО (32,1 против 13,2%, р = 0,005) на фоне комбинированной терапии афатинибом и паклитакселом [17,18]. Афатиниб в комбинации с паклитак-селом улучшал ВБП и ЧОО по сравнению с монохимиоте-рапией у пациентов с приобретенной резистентностью к эрлотинибу/гефитинибу и прогрессированием заболевания на фоне терапии афатинибом после первоначальной эффективности.…”

Targeted Therapy of NSCLC With Egfr Activating Mutations Improves the Quality of Life of Patients

“…Общее состояние здоровья/КЖ достоверно не различа-лось в группе афатиниб/паклитаксел, несмотря на удвое-ние средней длительности лечения по сравнению с груп-пой химиотерапии [34].…”