Squamous NSCLC

Real-world evidence: afatinib after chemo-immunotherapy in squamous NSCLC

A retrospective chart review evaluated treatment outcomes in patients (N=200) in US centers with metastatic squamous non-small cell lung cancer (NSCLC) who progressed on first-line immunotherapy plus chemotherapy.1 The patient population was heterogeneous in terms of histology (squamous or mixed) and EGFR mutation status. One group received second-line afatinib* (n=99); the other group received second-line chemotherapy (n=101).1 No direct comparisons between the afatinib and chemotherapy groups were planned.1

All 6 (6%) patients who had a Grade 3/4 immune-related adverse event (irAE) during second-line afatinib treatment had previously experienced a Grade 3/4 irAE during first-line therapy; there were no new safety signals with afatinib in this setting.1

Median time on treatment was 7.3 months (95% confidence interval [CI]: 5.2–8.1) in the afatinib group and 4.2 months (95% CI: 3.9–4.9) in the chemotherapy group.1

Among patients with squamous histology, median time on treatment was 5.8 months (95% CI: 4.4–8.0) in the afatinib group (n=64) and 4.2 months (95% CI: 3.8–4.8) in the chemotherapy group (n=98).1 Among patients with mixed histology, median time on treatment was 8.1 months (95% CI: 5.5–9.9) in the afatinib group (n=35) and not reached (95% CI: 3.2 months–not reached) in the chemotherapy group (n=3).1

Among patients with EGFR mutations, median time on treatment was 7.4 months (95% CI: 5.6–8.6) in the afatinib group (n=39); most patients had unknown EGFR mutation status (n=63) or were EGFR mutation-negative (n=33) in the chemotherapy group.1

In the chemotherapy group, patients received a variety of different regimens, indicating a lack of a clear standard of care in this setting.1

Findings from this study suggest that second-line afatinib is generally well tolerated and effective in patients with metastatic squamous NSCLC after failure of first-line chemo-immunotherapy.1 EGFR mutation testing could also help ensure that the most appropriate second-line treatment is selected.1

ErbB mutations in patients with squamous NSCLC

The LUX-Lung 8 trial demonstrated clinical benefit with afatinib versus erlotinib in the second-line treatment of a broad patient population with advanced squamous non-small cell lung cancer  (NSCLC).2

With the objective of identifying specific populations that might obtain particular benefit from second-line afatinib, Goss and colleagues explored ErbB Family mutations as potential oncogenic drivers in patients from the LUX-Lung 8 trial with squamous NSCLC.3 Next-generation sequencing revealed a relatively high prevalence of ErbB Family mutations in patients with squamous NSCLC, 53 of 245 patients (21.6%).3 In this subpopulation, progression-free survival (PFS) and overall survival (OS) were longer with afatinib than erlotinib in patients with ErbB wild-type tumors (median PFS: 3.5 vs 2.5 months; hazard ratio[HR]=0.69, 95% CI: 0.51–0.92; p=0.012 and median OS: 8.4 vs 6.6 months; HR=0.81, 95% CI: 0.62–1.05; p=0.115).3 Afatinib treatment effects were more pronounced in patients with ErbB mutation-positive squamous NSCLC than in those without ErbB mutations (median PFS: 4.9 vs 3.0 months; HR=0.62, 95% CI: 0.37–1.02; p=0.062 and median OS: 10.6 vs 8.1 months; HR=0.75, 95% CI: 0.47–1.17; p=0.206, respectively).3 The most marked treatment differences were seen in 12 patients with HER2 mutations, in whom the presence of HER2 mutations predicted more favorable outcomes with afatinib than erlotinib in terms of both PFS (interaction p value = 0.006) and OS (interaction p value = 0.003).3

Overall, the authors concluded that the role of ErbB mutations in squamous lung cancer may warrant further investigation, particularly in patients with HER2 mutations.3  In a related commentary in JAMA Oncology, Professor Gandara and colleagues endorse this conclusion, particularly in light of the lack of targeted therapies available for patients with advanced squamous lung cancers and the increasing use of broad-based next-generation sequencing at time of NSCLC diagnosis, regardless of histology or smoking status.4



Kim ES, et al. Presented at IASLC North America Conference on Lung Cancer 2020 (Abstract MO01.14).


Soria J-C, et al. Lancet Oncol 2015;16(8):897‒907.


Goss GD, et al. JAMA Oncol 2018;4(9):1189‒97.


Gandara DR, et al. JAMA Oncol 2018;4(9):1197‒8.

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*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 click here. Registration conditions differ internationally; please refer to locally approved prescribing information.


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Page last updated: December 2020