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Published on: September 25, 2018
Non-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation
Nadine Abdallah1, Misako Nagasaka2,3, Eman Abdulfatah4
1Department of Internal Medicine, Wayne State University, Detroit, MI 48201, USA.
Introduction:
Histologic transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a well-recognized mechanism of resistance in EGFR-mutant adenocarcinoma upon treatment with TKIs, but rarely reported with programmed death1 (PD-1) inhibitors. We report two cases of potential transformation during treatment with PD-1 inhibitors.
Case Presentations:
Case 1, a 65-year-old man was diagnosed with stage IVa lung adenocarcinoma on pleural fluid cytology. He received six cycles of carboplatin and pemetrexed, then maintained on pemetrexed. He had disease progression after nine cycles of pemetrexed and was switched to nivolumab. He progressed after five cycles of nivolumab. Core biopsy of the lung mass revealed SCLC. Case 2, a 68-year-old man was diagnosed with two primary NSCLCs and underwent resection. He had recurrence after several months and was treated with four cycles of carboplatin, paclitaxel, and pembrolizumab on clinical trial, with partial response. He was continued on pembrolizumab and had disease progression after 30 cycles. Biopsy of the new lesions showed SCLC.
Discussion:
Histologic transformation from NSCLC to SCLC can be explained by the presence of a common cell precursor. Proposed molecular mechanisms include loss of RB1, TP53 mutations, and MYC amplification. The distinction between transformation and mixed histology tumors is challenging, especially when pathologic material used for the initial diagnosis is limited. The possibility of a second metachronous primary lung cancer cannot be excluded in our cases.
Conclusion:
Histologic transformation with PD-1 inhibitors could be under-recognized. Disease progression should prompt re-biopsy to uncover new histology and change in treatment. Future studies are needed to elucidate mechanisms and predictors of transformation.
Insights
Histologic transformation from non-small cell lung cancer to small cell lung cancer during programmed death-1 inhibitor therapy is rare. Re-biopsy is crucial for identifying new histology and guiding treatment changes in lung cancer patients.
Area of Science:
- Oncology
- Cancer Biology
- Immunotherapy
Background:
- Histologic transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a known resistance mechanism to tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung adenocarcinoma.
- This transformation is rarely reported during treatment with programmed death-1 (PD-1) inhibitors.
Purpose of the Study:
- To report two cases of potential histologic transformation from NSCLC to SCLC during PD-1 inhibitor therapy.
- To highlight the importance of re-biopsy in cases of suspected transformation.
Main Methods:
- Case 1: A patient with lung adenocarcinoma treated with chemotherapy and subsequently nivolumab (a PD-1 inhibitor) who showed progression and biopsy-confirmed SCLC.
- Case 2: A patient with two primary NSCLCs treated with chemotherapy and pembrolizumab (a PD-1 inhibitor) who progressed and had biopsy-confirmed SCLC.
Main Results:
- Two cases of NSCLC transforming to SCLC during PD-1 inhibitor treatment are presented.
- The findings suggest that histologic transformation may occur with PD-1 inhibitors, potentially being under-recognized.
Conclusions:
- Histologic transformation from NSCLC to SCLC may be driven by common cell precursors and molecular alterations like RB1/TP53 loss or MYC amplification.
- Distinguishing transformation from mixed histology or secondary primaries is challenging.
- Prompt re-biopsy upon disease progression during PD-1 inhibitor therapy is essential to detect new histology and adjust treatment strategies.
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