Post-Progression Erlotinib Therapy ‘Feasible’ in EGFR Mutation-Positive NSCLC

Continuation of erlotinib treatment after progression could delay salvage therapy in non-small-cell lung cancer patients harbouring epidermal growth factor receptor mutations

medwireNews: Phase II trial results suggest that erlotinib treatment beyond disease progression could benefit Asian patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).

Researcher Keunchil Park, from Sungkyunkwan University School of Medicine in Seoul, Korea, and team say that continued exposure to the tyrosine kinase inhibitor (TKI) after progression as defined by the RECIST 1.1 criteria is “feasible and may be of benefit in delaying salvage anticancer therapy with no undue toxic effects in selected patients; however, validation in a randomized trial would be beneficial.”

Of the 207 stage IV or recurrent NSCLC patients with activating EGFR mutations included in the ASPIRATION (Asian Pacific trial of Tarceva as first-line in EGFR mutation) trial, 171 progressed after first-line erlotinib 150 mg/day, with a median progression-free survival (PFS)1 of 10.8 months.

Among those with progressive disease, over half (54%) continued to receive erlotinib at the investigator’s discretion, according to the report published in JAMA Oncology.

In this group, PFS2 – defined as the time from the initial study dose to off-erlotinib progressive disease – was a median of 14.1 months. And a post hoc exploratory analysis of patients who continued with erlotinib showed that median PFS1 was 11.0 months, giving a difference of 3.1 months. The investigators admit, however, that perhaps a more useful definition of PFS2 would have been the time from initial to second progression.

Moreover, median overall survival (OS) was 33.6 months for the participants who continued erlotinib therapy, compared with 22.5 months for those who did not. But the authors caution that this was a post hoc exploratory analysis and “could be biased by patient selection”.

Nonetheless, they conclude: “This provides further foundation for the current National Comprehensive Cancer Network clinical guidelines of recommending continuation of EGFR TKI with or without local therapy following either asymptomatic progression or symptomatic but oligometastasis.”

In an accompanying editorial, David Gandara, from UC Davis Comprehensive Cancer Center in Sacramento, California, USA, and co-authors note that although the article adds to the available literature, it also adds to “the confusion about what the right approach is”.

Questioning the advantages of delaying salvage therapy, they write: “In view of multiple viable choices for second-line therapy of EGFR-mutated lung cancer, the rationale for continuing the initial TKI therapy to delay salvage therapy has largely been obviated in those patients with systemic [progressive disease].”

Furthermore, the editorialists comment that the “potential for tremendous bias” resulting from the lack of randomisation makes the trial conclusions “tenuous at best”.

David Gandara et al conclude that hampered as it is by its study design, the ASPIRATION trial is “unable to fully address the most important question facing practicing oncologists: “What do I do with the next patient in my waiting room with [progressive disease] after initial TKI therapy of EGFR-mutated lung cancer”?”


Park K, Yu C-J, Kim S-W, et al. First-Line Erlotinib Therapy Until and Beyond Response Evaluation Criteria in Solid Tumors Progression in Asian Patients With Epidermal Growth Factor Receptor Mutation–Positive Non–Small-Cell Lung Cancer. The ASPIRATION Study.JAMA Oncol; Advance online publication 30 December 2015. doi:10.1001/jamaoncol.2015.4921

Gandara DR, Redman M, Hirsch FR. Postprogression Prolongation of Survival in EGFR-Mutated Lung Cancer. Reconciling the ASPIRATION and IMPRESS Trials. JAMA Oncol; Advance online publication 30 December 2015. doi:10.1001/jamaoncol.2015.4920

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