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Small Cell Lung Cancer Transformation as a Mechanism of Resistance to PD-1 Therapy in KRAS-Mutant Lung Adenocarcinoma: A Report of Two Cases  Wade T.

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Presentation on theme: "Small Cell Lung Cancer Transformation as a Mechanism of Resistance to PD-1 Therapy in KRAS-Mutant Lung Adenocarcinoma: A Report of Two Cases  Wade T."— Presentation transcript:

1 Small Cell Lung Cancer Transformation as a Mechanism of Resistance to PD-1 Therapy in KRAS-Mutant Lung Adenocarcinoma: A Report of Two Cases  Wade T. Iams, MD, Kathryn E. Beckermann, MD, PhD, Karinna Almodovar, PhD, Jennifer Hernandez, BS, Cindy Vnencak-Jones, PhD, Lee P. Lim, PhD, Christopher K. Raymond, PhD, Leora Horn, MD, Christine M. Lovly, MD, PhD  Journal of Thoracic Oncology  Volume 14, Issue 3, Pages e45-e48 (March 2019) DOI: /j.jtho Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions

2 Figure 1 Case 1. Chronological summary of therapies, imaging studies, and available pathologic findings from diagnosis of adenocarcinoma to transformation to small cell carcinoma. (A) The patient received four cycles of carboplatin and paclitaxel (C/P) followed by a 17-month therapy holiday. She then received 36 cycles of nivolumab every 2 weeks with an initial response, and 2 weeks after her 36th dose of nivolumab she had widespread disease progression, with a biopsy revealing transformation to small cell carcinoma. She went on to receive six cycles of carboplatin and etoposide (C/E) and had a partial response. Two months after completion of C/E therapy she had disease progression and received eight cycles of paclitaxel with a response in her thoracic disease, but she had progression in the central nervous system after her death 11 months after the small cell transformation. (B) Treatment responses were observed in the primary right upper lobe nodule (red arrow) to both carboplatin and paclitaxel and nivolumab, followed by widespread progression, including in the right upper lobe nodule (red arrow), at the time of transformation to small cell carcinoma. (C) Pathologic findings from a level 4R lymph node at the time of diagnosis demonstrated poorly differentiated adenocarcinoma. Cytologic examination of the pericardial fluid at the time of transformation demonstrated small cell carcinoma that was confirmed by synaptophysin immunohistochemistry. Journal of Thoracic Oncology  , e45-e48DOI: ( /j.jtho ) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions

3 Figure 2 Case 2. Chronological summary of therapies, imaging studies, and available pathologic findings from diagnosis of adenocarcinoma to transformation to small cell carcinoma. (A) The patient received six cycles of carboplatin, pemetrexed, and bevacizumab (C/P/B), followed by seven cycles of pemetrexed and bevacizumab (P/B) maintenance therapy. She experienced disease progression after a 16-month therapy holiday. She received 33 cycles of second-line nivolumab with disease stabilization, and after an 11-month therapy holiday she progressed with transformation to small cell carcinoma. She received four cycles of carboplatin and etoposide (C/E) with disease stabilization and then experienced disease progression 4 months after completion of C/E therapy. She received three cycles of nivolumab and ipilimumab (N/I) with disease progression, after which she received 10 cycles of irinotecan (I) with initial disease stabilization. After 10 cycles of irinotecan she had further disease progression; she then transitioned to hospice care, dying 16 months after small cell transformation. (B) The patient’s disease was primarily measured by upper lobe ground glass opacities. She experienced a partial response (according to the Response Criteria in Solid Tumors) with first-line therapy, followed by disease stabilization while she was receiving second-line nivolumab. She had asymptomatic diffuse progression of her bilateral ground glass opacities at the time of transformation to small cell carcinoma. (C) Pathologic findings from a left lower lobe lesion at the time of diagnosis demonstrated lung adenocarcinoma. Pathologic findings from a right lower lobe lesion at the time of first progression revealed lung adenocarcinoma consistent with the prior diagnosis. Pathologic findings from a station 7 lymph node at the time of second progression demonstrated small cell carcinoma that was confirmed by synaptophysin immunohistochemistry. Journal of Thoracic Oncology  , e45-e48DOI: ( /j.jtho ) Copyright © 2018 International Association for the Study of Lung Cancer Terms and Conditions

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