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Shikha Jain
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EP1.04 - Immuno-oncology (ID 194)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.04-12 - Response to Combination of Metformin and Nivolumab in a NSCLC Patient Whose Disease Previously Progressed on Nivolumab (Now Available) (ID 2899)
08:00 - 18:00 | Author(s): Shikha Jain
- Abstract
Background
Beyond metformin’s success as a widely used anti-diabetic, there is mounting evidence for its anti-cancer properties. Metformin disrupts many molecular pathways, in particular causing mTOR inhibition. Additionally, it causes metabolic alterations that might impact cancer cell survival. Recent experiments have also suggested that metformin has immune modulatory properties. Metformin impairs immunologic exhaustion of CD8+ lymphocytes, potentiating immune response to tumors. Thus, when curbing acquired resistance to immune checkpoint inhibition, adding metformin could prove to be a valid strategy. Here, we present a case of a NSCLC patient for whom the addition of metformin coincided with reversal of disease progression on a single-agent nivolumab.
Method
This is a case report obtained by medical records revision.
Result
Case report: A 75-year-old male, ex-smoker, initially presented with symptomatic left pleural effusion and multiple lung nodules 7 years ago. Pathology confirmed poorly differentiated adenocarcinoma, wild-type for molecular targets. Disease was Stage IV based on the presence of a malignant pleural infusion. The patient underwent VATS and left pleurodesis and was started on systemic therapy. After four cycles of pemetrexed-platinum doublet, he was put on maintenance chemotherapy with clinical response but, eventually, maintenance treatment was discontinued due to worsening fatigue. The patient developed significant disease progression resulting in a left peripheral mass adjacent to the cardiac silhouette. He then underwent localized SBRT followed by disease stability for approximately 6 months. 48 months ago, the patient developed progressive disease and was briefly put on vinorelbine. Due to toxicity and worsening kidney function, the treatment was stopped after one cycle. One month later, the patient started the immune checkpoint inhibitor, nivolumab. In the first imaging assessment there was evidence of response to immunotherapy and that was followed by disease control for 10 months. After that, asymptomatic lung and pleural progression ensued. Initial decision was made to continue nivolumab. Repeat scans revealed continued interval increases in the lung nodules. Metformin XR 2000mg PO daily was added to the treatment regimen. Since then, the patient has been tolerating the combination treatment well and new response was observed in the following scans with interval diminishing of the lung nodules followed by on-going stability for 17 months.
Conclusion
There has been some evidence that metformin can enhance anti-PD-1/PD-L1 activity. We here presented a case of metastatic lung adenocarcinoma with long-term disease stability coinciding with the addition of metformin to nivolumab regimen. A new phase-2 clinical trial (NU16L04) open in our institution has been accruing NSCLC patients, including those previously refractory to anti-PD-1/PD-L1 to receive nivolumab and metformin combination.
