Stage 4 lung adenocarcinoma: complete response on immunotherapy combination

What happened, in summary

A male current smoker with a 50 pack-year history presented with nodules in both lungs and a suspicious left adrenal gland lesion. Biopsy confirmed metastatic lung adenocarcinoma, making this Stage IV disease. The biopsy tissue was limited, so PD-L1 expression could not be meaningfully assessed. Molecular testing was performed on both tissue and circulating tumor DNA. Tissue testing found no targetable mutations but did identify TP53 and ARID1A mutations. Liquid biopsy confirmed the tissue findings and detected additional alterations in TP53, ARID1A, KEAP1, MAP2K, and SMARCA4. Because no mutation pointed to targeted therapy, treatment began with carboplatin, pemetrexed, and pembrolizumab. He had an immediate excellent clinical response and a complete radiologic response. After 4 cycles, carboplatin and pemetrexed were stopped, and pembrolizumab continued every 3 weeks as maintenance therapy. The deep response lasted more than 14 months on pembrolizumab alone. A later routine CT scan showed a new 1.2-cm subpleural nodule in the lingula, while the original primary and metastatic sites remained controlled. PET scan showed the new nodule was FDG-avid with SUVmax 6.2, raising concern for recurrent malignancy, but no other distant sites were found. Circulating tumor DNA testing detected no somatic variants, including clearance of previously seen alterations. Because imaging looked suspicious while the blood test and clinical status were reassuring, the nodule was biopsied. Pathology showed necrotizing granulomatous inflammation, not cancer. As of May 2024, no further intervention was needed for that nodule, and he remained well on pembrolizumab with no further evidence of progression.