Date Published: April 11, 2019
Publisher: Public Library of Science
Author(s): Paul Germonpré, Tim Van den Wyngaert, Giandomenico Roviello.
Little data is available on patients with advanced non-squamous NSCLC treated with erlotinib specifically after failure of first-line pemetrexed-containing chemotherapy. We assessed the effectiveness, safety and tolerability of erlotinib in a real-world setting.
Prospective single-arm, open-label, multicenter, non-interventional study of erlotinib (150mg daily) in inoperable stage III/IV NSCLC after progression on first-line pemetrexed-containing chemotherapy without EGFR-mutation selection. Patients were followed according to routine practice and response assessment was performed using RECIST 1.1. The primary end point was progression-free survival (PFS). Secondary end points included best confirmed overall response rate (ORR), disease control rate (DCR), and overall survival (OS). Adverse events were recorded. An independent dataset was used to validate the results.
In all, 59 patients were screened, 57 enrolled, and 54 (36 men; median age 65 years) included in the per-protocol analysis. Median PFS was 1.8 (95% CI 1.4–2.6) months, with 11% (95% CI 5–21%) alive and progression-free at 6 months. The ORR was 0.0% (97.5% CI 0.0–6.8%) and the DCR 34.6% (95% CI 21.9–49.0%). Median overall survival was 5.8 (95% CI 3.3–8.6) months with 28% (95% CI 17–42%) alive at one year. Rash occurred in 60.7% (95% CI 46.7–73.5%), with severe rash in 12.5% (95% CI 5.1–24.1%). Any grade diarrhea was observed in 42.8% (95% CI 29.7–56.8%), with grade 3 occurring in 7.1% (95% CI 1.9–17.2%). Erlotinib was stopped in 21.0% (95% CI 11.3–33.9%) of patients due to adverse events, which were treatment related in 7%.
Second-line erlotinib after pemetrexed treatment results in similar real-world outcomes as reported after non-pemetrexed containing first-line therapy. However, the overall duration of response in unselected patients remains limited and other effective treatments have in the meantime been introduced. No new safety signals were detected.
With an estimated 279.400 deaths in Europe in 2015, lung cancer remains the most frequent and lethal cancer in men and has equaled breast cancer mortality in woman. Treatment options for non-small cell lung cancer (NSCLC), which accounts for approximately 80% of all lung cancers, have increased considerably over the last decade, yet it still remains a largely fatal disease. In addition, the benefit of most novel treatment options is conditional on the presence of specific tumor biomarkers associated with response (e.g. expression of programmed death ligand 1 [PD-L1], or particular gene mutations or rearrangements). Erlotinib is an oral highly potent reversible tyrosine kinase inhibitor (TKI) that targets the Human Epidermal Growth Factor Receptor Type 1 (HER1)/Epidermal Growth Factor Receptor (EGFR). In Europe, erlotinib is approved for the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR activating mutations, for switch maintenance treatment in patients with locally advanced or metastatic NSCLC with EGFR activating mutations and stable disease after first-line chemotherapy. Also, erlotinib is indicated for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen: if a positive EGFR-expression is demonstrated on immunohistochemistry, or in disease without EGFR activating mutations if other treatment options are not considered suitable.
The expanding number of available therapies in locally advanced or metastatic NSCLC provides unique challenges, in particular with respect to outcome data on specific treatment sequences. The EGFR targeted tyrosine kinase inhibitors (TKI) erlotinib, afatinib or gefitinib are available as second-line treatments, although the latter two may only be available in some regions and limited to patients with a tumor bearing an activating EGFR mutation. These anti-EGFR TKIs have demonstrated a favorable hematologic toxicity profile (e.g. less grade 3–4 neutropenia and thrombocytopenia) compared to the chemotherapeutic alternatives and can provide a treatment alternative in patients in whom a break from chemotherapy is preferred.[4, 20, 21]
Second-line erlotinib after progression on pemetrexed results in similar real-world outcomes as reported after non-pemetrexed containing first-line treatments. However, the overall duration of response in unselected patients remains limited, as observed with other EGFR targeting agents, and other effective treatments have in the meantime been introduced. Adverse events were similar to the established safety profile of erlotinib, with rash and diarrhea being very common, but mostly of mild or moderate severity.