Real World Data Show Afatinib as Effective, Safe in Second-Line Metastatic Squamous Lung Cancer

Edward S. Kim, MD

Afatinib (Gilotrif) was found to be effective and well tolerated when used as a second-line treatment in patients with metastatic squamous carcinoma of the lung, according to real-world data from a retrospective chart review trial presented during the 2020 IASLC North America Conference on Lung Cancer.^1,2

Results showed that the overall median time on treatment for patients who received second-line afatinib was 7.3 months (95% CI, 5.2-8.1). Additionally, severe immune-related toxicities were reported in 6 patients and included pneumonitis (n = 3), colitis (n = 2), and hepatitis (n = 1). All of these patients had previous grade 3 or 4 toxicities during first-line treatment, all had squamous histology, and 1 had EGFR positivity.

Second-line chemotherapy was also examined in this setting and results revealed a median overall time on treatment of 4.2 months (95% CI, 3.9-4.9). No immune-related adverse effects (AEs) were observed in this cohort.

“Given relatively recent advances with immunotherapy, prospective trials have yet to investigate the use of afatinib following first-line immunotherapy and chemotherapy in metastatic squamous cell carcinoma of the lung when pembrolizumab (Keytruda) is added to first-line platinum-based chemotherapy,” said Edward S. Kim, MD, chair of the Solid Tumor Oncology and Investigational Therapeutics and Donald S. Kim Distinguished Chair for Cancer Research at the Levine Cancer Institute.² “Findings from this study suggest that second-line afatinib is generally well tolerated and effective in patients with metastatic squamous cell carcinoma of the lung when pembrolizumab is added to first-line platinum-based chemotherapy.”

Pembrolizumab in combination with chemotherapy is FDA approved for the frontline treatment of patients with metastatic squamous NSCLC, and afatinib is indicated for use following platinum-based chemotherapy.1 To date, no prospective trials have evaluated the use of the TKI after frontline chemoimmunotherapy for metastatic squamous disease.

In the retrospective, non-interventional, multisite cohort, real-world trial, investigators set out to characterize the profiles and outcomes of patients who progressed on frontline immunotherapy in combination with platinum-based chemotherapy and went on to receive afatinib as second-line treatment.

To do this, US-based community oncologists identified patients that met the criteria and data were pulled from electronic health records. The analysis looked at 2 different patient cohorts. Patients with advanced or metastatic squamous/mixed histology NSCLC received frontline pembrolizumab in combination with platinum-based chemotherapy, followed by either afatinib (cohort 1) or chemotherapy (cohort 2). Primary outcomes incorporated patient demographics and clinical features, the incidence of severe immune-related AEs, and time on treatment.

A total of 200 patients were included in the analysis; 99 of these patients comprised cohort 1, while 101 of these patients comprised cohort 2. In cohort 1, 64.6% of patients had squamous cell histology, while 35.4% had mixed histology; these rates were 97.0% versus 3.0%, respectively, in cohort 2. Additionally, 39.4% of those who received second-line afatinib had EGFR positivity versus 5.0% of those who received chemotherapy. The majority of patients in both cohorts were white. In the afatinib cohort, 45.5% of patients had an ECOG performance status ranging from 0 to 1, while 54.5% had a status of 2 or higher. In the chemotherapy arm, 49.5% of patients had a status of 0 to 1 and 50.5% had a status of 2 or higher.

At the time of data cutoff, 53.5% of those who received second-line afatinib were still receiving treatment versus 40.6% of those given second-line chemotherapy. Moreover, 9.1% versus 8.9% of patients in the afatinib and chemotherapy cohorts, respectively, discontinued second-line treatment and received no further therapy; 4.0% versus 5.0% of patients, respectively, initiated third-line treatment. Less patients (n = 33) died in cohort 1 versus cohort 2 (n = 46).

“These real-world data suggest that second-line afatinib is generally well tolerated and effective in patients with metastatic squamous carcinoma of the lung; they provide rationale for further evaluation of second-line afatinib treatment following first-line pembrolizumab plus platinum-based chemotherapy in this patient group,” the authors concluded in the abstract. “A high proportion of [patients with] EGFR[-mutated disease] received first-line immunotherapy rather than an EGFR TKI, highlighting the importance of testing.”

References

1. Kim ES, Subramanian J, Kish J, et al. Real-world effectiveness and safety of afatinib following immunotherapy (IO) in the treatment of metastatic, squamous cell/mixed histology carcinoma of the lung: a multi-site retrospective chart review trial in the US. Presented at: 2020 IASLC North America Conference on Lung Cancer; October 16-17, 2020; Virtual. Abstract MO01.14.
2. IASLC NACLC 2020: Boehringer Ingelheim presents new data for Gilotrif in metastatic, squamous cell carcinoma of the lung, and in EGFR mutation-positive NSCLC. News release. Boehringer Ingelheim. October 13, 2020. Accessed October 20, 2020. https://bit.ly/3m6xUBx.