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Case Reports
. 2018 Jan;9(1):175-180.
doi: 10.1111/1759-7714.12543. Epub 2017 Oct 24.

Remarkable response of nivolumab-refractory lung cancer to salvage chemotherapy

Daiki Ogawara  1 , Hiroshi Soda  1 , Keisuke Iwasaki  2 , Takayuki Suyama  1 , Hirokazu Taniguchi  1   3 , Yuichi Fukuda  1 , Hiroshi Mukae  3
Affiliations
Case Reports

Remarkable response of nivolumab-refractory lung cancer to salvage chemotherapy

Daiki Ogawara et al. Thorac Cancer. 2018 Jan.

Abstract

Promising outcomes of salvage chemotherapy after nivolumab therapy have been reported; however, little is known about the detailed clinical and immunologic features in lung cancer patients in whom nivolumab is unsuccessful. We report two cases of nivolumab-refractory lung cancer, in which chemotherapy resulted in rapid regression of the lung cancer. Upon initial diagnosis, the biopsy specimens showed PD-ligand 1 (PD-L1)-expressing cancer cells, accompanied by tumor-infiltrating lymphocytes with a favorable CD8/CD4 ratio. Immunosuppressive regulatory T cells and cells positive for TIM-3 were also observed. Physicians should take caution in treating lung cancer patients after progression on nivolumab. Further studies with a large cohort are warranted to identify the patients that may benefit from salvage chemotherapy.

Keywords: Chemotherapy; immunotherapy; non-small cell lung cancer.

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Figures

Figure 1
Figure 1
Chest computed tomography scans of a patient with undifferentiated non‐small cell lung cancer. (a) Before treatment with nivolumab, a 28 mm tumor is seen in the left lower lobe of the lung. (b) After nine courses of nivolumab therapy, the diameter of the lung tumor increased to 55 mm. (c) After treatment with two courses of S−1, the lung tumor decreased to 20 mm in diameter.
Figure 2
Figure 2
Photomicrographs of a transbronchial biopsy specimen of a patient with undifferentiated non‐small cell lung cancer. (a) Large, undifferentiated cancer cells are seen in the fibrous tissue (hematoxylin & eosin stain, original magnification 400×). (b) Immunohistochemical examination shows that > 90% of the tumor cells expressed programmed death ligand‐1 at a high intensity (original magnification 400×).
Figure 3
Figure 3
Immunohistochemical profiles of the tumor‐infiltrating lymphocytes in a patient with undifferentiated non‐small cell lung cancer. (a) CD3+ lymphocytes, (b) CD8+ cells, (c) CD4+ cells, (d) FOXP3+ regulatory T‐cells, and (e) TIM‐3+ cells are seen in the tumor stroma (original magnification 100×). The antibody clones used are as follows: CD3 (F7.2.38), CD8 (4B11), CD4 (4B12), FOXP3 (236A/E7), and TIM‐3 (D5D5R).
Figure 4
Figure 4
Chest computed tomography scans of a patient with lung adenocarcinoma. Before treatment with nivolumab, (a) a 45 mm primary tumor is observed in the left lower lobe of the lung. (b) After six courses of nivolumab therapy, the primary lung tumor increased to 75 mm in diameter. (c) After two courses of carboplatin/albumin‐bound paclitaxel therapy, the primary lung tumor decreased to a diameter of 25 mm.
See this image and copyright information in PMC

References

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