EGFR-mutant NSCLC may still respond to PD-1 blockade

PD-1 blockade should still be considered as a second-line approach in patients with EGFR-mutant non–small-cell lung cancer (NSCLC), as some may still respond to this therapy, investigators reported.

The researchers described a patient who was diagnosed with epidermal growth factor receptor (EGFR)-mutant NSCLC but who also showed high expression of PD-L1.

The 62-year-old woman first presented with a lung nodule and metastasis in the right hip, which were EGFR-mutant and had a PD-L1 tumor proportion score of 90%. She was treated with erlotinib – an EGFR tyrosine kinase inhibitor – and radiotherapy, according to the report, published in Annals of Oncology.

Two months later, she developed multiple new metastases in the chest wall. These also showed high PD-L1 expression, but no EGFR mutations, so she was treated with pembrolizumab as second-line therapy.

After the first course of treatment with pembrolizumab, the hip pain improved dramatically, and after three cycles the primary and metastatic lesions disappeared completely.

“Immunofluorescent analysis of both right ilium and chest wall lesions with an anti-EGFR antibody specific to Ex.19 del and an anti-PD-L1 antibody revealed the presence of distinct heterogeneity of EGFR-mutant clones and PD-L1 highly-expressing clones,” wrote Kei Kunimasa, MD, of Osaka International Cancer Institute, and coauthors.

Current clinical trials suggested that patients with EGFR mutations are likely to have a poor response to PD-1 blockade therapies for NSCLC, and the authors agreed that patients with EGFR mutations should be treated with EGFR tyrosine kinase inhibitors as first-line therapy.

“However, the present case suggested that shorter PFS in EGFR-TKI treatment for EGFR-mutant NSCLC patients with high PD-L1 TPS and without acquired T790M mutation could encourage us to try PD-1 blockade therapy as second line therapy,” they wrote.

The investigators suggested that certain clinical factors could identify patients with EGFR-mutant NSCLC who might respond well to PD-1 blockade, such as progression-free survival on EGFR tyrosine kinase inhibitor treatment, other targetable resistant mutations, tumor mutation burden, and PD-L1 expression.

Two authors reported grants and personal fees from pharmaceutical companies outside the submitted work. No other conflicts of interest were declared.

SOURCE: Kunimasa K et al. Ann Oncol, 2018 Aug 7. doi: 10.1093/annonc/mdy312.

PD-1 blockade should still be considered as a second-line approach in patients with EGFR-mutant non–small-cell lung cancer (NSCLC), as some may still respond to this therapy, investigators reported.

The researchers described a patient who was diagnosed with epidermal growth factor receptor (EGFR)-mutant NSCLC but who also showed high expression of PD-L1.

The 62-year-old woman first presented with a lung nodule and metastasis in the right hip, which were EGFR-mutant and had a PD-L1 tumor proportion score of 90%. She was treated with erlotinib – an EGFR tyrosine kinase inhibitor – and radiotherapy, according to the report, published in Annals of Oncology.

Two months later, she developed multiple new metastases in the chest wall. These also showed high PD-L1 expression, but no EGFR mutations, so she was treated with pembrolizumab as second-line therapy.

After the first course of treatment with pembrolizumab, the hip pain improved dramatically, and after three cycles the primary and metastatic lesions disappeared completely.

“Immunofluorescent analysis of both right ilium and chest wall lesions with an anti-EGFR antibody specific to Ex.19 del and an anti-PD-L1 antibody revealed the presence of distinct heterogeneity of EGFR-mutant clones and PD-L1 highly-expressing clones,” wrote Kei Kunimasa, MD, of Osaka International Cancer Institute, and coauthors.

Current clinical trials suggested that patients with EGFR mutations are likely to have a poor response to PD-1 blockade therapies for NSCLC, and the authors agreed that patients with EGFR mutations should be treated with EGFR tyrosine kinase inhibitors as first-line therapy.

“However, the present case suggested that shorter PFS in EGFR-TKI treatment for EGFR-mutant NSCLC patients with high PD-L1 TPS and without acquired T790M mutation could encourage us to try PD-1 blockade therapy as second line therapy,” they wrote.

The investigators suggested that certain clinical factors could identify patients with EGFR-mutant NSCLC who might respond well to PD-1 blockade, such as progression-free survival on EGFR tyrosine kinase inhibitor treatment, other targetable resistant mutations, tumor mutation burden, and PD-L1 expression.

Two authors reported grants and personal fees from pharmaceutical companies outside the submitted work. No other conflicts of interest were declared.

SOURCE: Kunimasa K et al. Ann Oncol, 2018 Aug 7. doi: 10.1093/annonc/mdy312.

PD-1 blockade should still be considered as a second-line approach in patients with EGFR-mutant non–small-cell lung cancer (NSCLC), as some may still respond to this therapy, investigators reported.

The researchers described a patient who was diagnosed with epidermal growth factor receptor (EGFR)-mutant NSCLC but who also showed high expression of PD-L1.

The 62-year-old woman first presented with a lung nodule and metastasis in the right hip, which were EGFR-mutant and had a PD-L1 tumor proportion score of 90%. She was treated with erlotinib – an EGFR tyrosine kinase inhibitor – and radiotherapy, according to the report, published in Annals of Oncology.

Two months later, she developed multiple new metastases in the chest wall. These also showed high PD-L1 expression, but no EGFR mutations, so she was treated with pembrolizumab as second-line therapy.

After the first course of treatment with pembrolizumab, the hip pain improved dramatically, and after three cycles the primary and metastatic lesions disappeared completely.

“Immunofluorescent analysis of both right ilium and chest wall lesions with an anti-EGFR antibody specific to Ex.19 del and an anti-PD-L1 antibody revealed the presence of distinct heterogeneity of EGFR-mutant clones and PD-L1 highly-expressing clones,” wrote Kei Kunimasa, MD, of Osaka International Cancer Institute, and coauthors.

Current clinical trials suggested that patients with EGFR mutations are likely to have a poor response to PD-1 blockade therapies for NSCLC, and the authors agreed that patients with EGFR mutations should be treated with EGFR tyrosine kinase inhibitors as first-line therapy.

“However, the present case suggested that shorter PFS in EGFR-TKI treatment for EGFR-mutant NSCLC patients with high PD-L1 TPS and without acquired T790M mutation could encourage us to try PD-1 blockade therapy as second line therapy,” they wrote.

The investigators suggested that certain clinical factors could identify patients with EGFR-mutant NSCLC who might respond well to PD-1 blockade, such as progression-free survival on EGFR tyrosine kinase inhibitor treatment, other targetable resistant mutations, tumor mutation burden, and PD-L1 expression.

Two authors reported grants and personal fees from pharmaceutical companies outside the submitted work. No other conflicts of interest were declared.

SOURCE: Kunimasa K et al. Ann Oncol, 2018 Aug 7. doi: 10.1093/annonc/mdy312.