Afatinib was found to be effective and well tolerated when used as a second-line treatment in patients with metastatic squamous carcinoma of the lung.
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.”