Stage IV PD-L1-negative lung adenocarcinoma: complete response with nivolumab and ipilimumab

What happened, in summary

A 55-year-old heavy smoker was admitted in May 2022 with cough and shortness of breath. CT and PET imaging showed a large left hilar lung mass about 61 mm with main-bronchus narrowing and downstream atelectasis, another lower lung lesion, sub-carinal lymphadenopathy, left pleural effusion, and a right adrenal lesion. Endobronchial ultrasound-guided transbronchial needle aspiration confirmed lung adenocarcinoma. The cancer was PD-L1 negative. DNA and RNA next-generation sequencing found no molecular alteration suitable for targeted therapy and did identify a TP53 alteration reported at 66%. The overall picture was Stage IV metastatic non-small cell lung cancer, with pleural and adrenal involvement. Before treatment, repeat CT showed the left hilar lesion remained about 61 x 55 mm, the retrocardiac lesion had increased to 57 x 35 mm, and the right adrenal metastasis was stable at 44 mm. After discussing options, she started the CheckMate 9LA regimen in July 2022, chosen partly because it uses only 2 cycles of chemotherapy during induction and avoids maintenance chemotherapy. The first 4 cycles included 2 cycles of chemotherapy plus nivolumab and ipilimumab, followed by 2 cycles of nivolumab and ipilimumab. Reassessment showed partial response, with reduction of the left hilar lesion, regression of the pleural effusion, and disappearance of the lower lung lesion, sub-carinal lymphadenopathy, and adrenal lesion. She then continued nivolumab and ipilimumab maintenance. After 8 cycles, CT showed complete remission. As of February 2024, she had completed 14 cycles, remained on maintenance nivolumab and ipilimumab, had no significant toxicity, and had persistent complete response.