FDA-Approved Frontline Agent for Metastatic NSCLC May Be Effective as Second-Line Treatment of a Lung Cancer Subgroup

Afatinib (Gilotrif), an FDA-approved frontline treatment for patients with metastatic non–small cell lung cancer (NSCLC), has now demonstrated efficacy and tolerable safety in the second-line setting of metastatic squamous cell carcinoma of the lung, especially with the addition of pembrolizumab (Keytruda) in the frontline setting, according to new real-world data presented during the International Association for the Study of Lung Cancer (IASLC) 2020 North America Conference on Lung Cancer.¹

Findings in this regard were presented during by Edward. S. Kim, MD, FACP, chair, Department of Solid Tumor Oncology, Levine Cancer Institute, Atrium Health. The retrospective study reviewed data from 200 eligible patients, 99 of whom were treated with afatinib in the second-line setting and 101 of whom were treated with second-line chemotherapy. The co-primary end points were patient demographic and clinical characteristics, time on second-line treatment, and the incidence of severed immune-related adverse events (irAEs) defined as grade 3 or higher events.

“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 NSCLC,” said Kim, as a statement in a press release issued by Boehringer Ingelheim.²

The Real-World Patient Population

At baseline, the median age of patients was 68 years (range, 61-73) in the afatinib arm versus 66 years (range, 61-70) in the chemotherapy arm. The majority of patients in the study were male, who made up 57% of the afatinib arm and 66% of the chemotherapy arm. Patients mainly identified as White including 60% of the afatinib arm versus 72% of the chemotherapy arm, but the second most populous group were Black patients who accounted for 30% of the afatinib arm and 23% of the chemotherapy arm. Few patients who identified as Asian were enrolled, mostly in the afatinib arm (6%), but 1 patient did enroll in the chemotherapy arm. Finally, the Other category made of 4% of each arm.¹

Smoking history was taken for each patient in the study, and most patients were previous smokers, including 80% of the afatinib arm versus 89% of the chemotherapy arm. Sixteen percent of the patients in afatinib arm identified as current smokers compared with 19% of the chemotherapy population. Finally, 12% of the afatinib arm never smoked, but there were no patients in this category in the chemotherapy arm. Stage IV disease was diagnosed in 80% of the afatinib group versus 89% of the chemotherapy group, while the remaining patients were stage IIIB, 7% and 3%, respectively.

Other clinical characteristics showed that most of the patients in the afatinib arm (65%) had squamous histology and 39% were diagnosed with EGFR-mutant NSCLC, whereas almost all of the patients in the chemotherapy arm (97%) had squamous histology. Together, the 2 groups had an unknown EGFR mutation status in 47.5% of patients.

The duration of frontline immunotherapy plus chemotherapy was median of 7.8 (95% CI, 6.6-9.1) in the afatinib arm compared with 8.2 months (95% CI, 7.0-8.7) in the chemotherapy arm. At the start of second-line therapy, baseline screening showed that 55% of patients in the afatinib arm had an ECOG performance status of ≥2 and 45% had a performance status of 0 or 1. In comparison, 50.5% of patients in the chemotherapy arm had a performance status ≥2, and 49.5% had a performance status of 0 or 1. The screening also revealed brain metastases in 14% of the afatinib population versus 10% of the chemotherapy population.

Incidence of iRAE Related to Second-line Therapy

During second-line therapy 6 patients experienced grade 3/4 iRAEs in the afatinib arm. All of these patients also previously experienced a grade 3/4 iRAE while on front-line treatment. The type of iRAE also appeared to be similar from the front line to the second line. The iRAEs observed were colitis, hepatitis, and pneumonitis.

Any-grade adverse reactions aside from IRAEs occurred in ≥5% who received second-line afatinib. The most common reactions were diarrhea (26%), skin rash (6%), stomatitis (5%), and fatigue (5%).

Differences in Duration of Treatment

The median time on treatment with afatinib was 7.3 months (95% CI, 5.2-8.1), which was significantly longer than treatment with chemotherapy, which lasted for a median of 4.2 months (95% CI, 3.9-4.9).

Longer time on treatment with afatinib was also observed across histologies. Specifically, the 35 patients with mixed histology had a median time on treatment of 8.1 months (95% CI, 5.5-9.9), which was longer compared with the 64 with squamous histology at 5.8 months (95% CI, 4.4-8.0).

Kim et al also compared patients with EGFR mutations to those without and found that the 39 patients with EGFR mutation had a median time of treatment of 7.4 months (95% CI, 5.6-8.6) compared with 5.9 months (95% CI, 4.4-not applicable).

Time on second-line chemotherapy was significantly less than afatinib treatment across histologies. Among the 3 patients with mixed histology, the median time on treatment was not reached ([NR], 95% CI, 3.2 to NR). For the 98 patients with squamous histology, the median time on treatment was 4.2 months (95% CI, 3.8-4.8), and for the 33 patients with EGFR mutations, the median time of on treatment was 5.1 months (95% CI, 3.5-5.6).

Taken together, these real-world data imply that oncologists should give further consideration to EGFR mutation mutations in patients with squamous cell carcinoma of the lung as patients with EGFR-mutant NSCLC appear to be a heterogenous population based on their tumor histology.

_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 the IASLC 2020 North America Conference on Lung Cancer Worldwide Virtual Event (NACLC 2020); October 16–17, 2020. 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 19, 2020. https://bit.ly/2FLtQY4}