Two new treatment approaches may significantly delay disease recurrence in patients with stage III non-small cell lung cancer (NSCLC). Interestingly, one approach involves an agent with a novel mechanism of action while the other involves an existing diabetes drug that may have a dual role in combating NSCLC. This research was presented at the 15th World Conference on Lung Cancer, held in late October, in Sydney, Australia.
Investigators from the University of Pennsylvania have found that patients with stage IIIA/B NSCLC who receive metformin for diabetes may have improvements in local control and overall survival (OS) compared with patients not taking metformin and with historical controls.1 Metformin, the most-widely used drug for type-2 diabetes, has been found to have benefit in treating a number of cancers, including prostate cancer and colon cancer. Now, researchers have discovered that this antidiabetic agent may be an effective radiosensitizing agent in combination with radiation therapy and chemotherapy.
“It has a great safety profile and it is right at our fingertips,” said lead study investigator Ildiko Csiki, MD, PhD, an assistant professor of radiation oncology at the University of Pennsylvania, Philadelphia, PA. “It is a very safe drug with a good history, and it is affordable.”
According to Dr. Csiki, metformin is thought to inhibit cancer growth by activating adenosine monophosphate-related pathways, leading to inactivation of mammalian target of rapamycin and suppression of its downstream effectors. In this current study, she and her team analyzed data from 760 consecutive patient treatment courses at a single institution between June 2008 and June 2013.
The researchers found that, with a median follow-up of 10.4 months, only two local recurrences had occurred among the 16 patients with diabetes.1 Dr. Csiki said that the patients with diabetes who received definitive chemoradiation for stage III NSCLC and were prescribed metformin had improved local control and OS compared with both patients not taking metformin and historical controls.
In addition, the 5-year survival rate for this patient population is approximately 15%; however, metformin may be able to slow tumor growth and recurrence and improve survival rates, noted Dr. Csiki.
“The results are very encouraging. Metformin can work directly and indirectly on cancer cells,” said Dr. Csiki in an interview with ChemotherapyAdvisor.com.
MK-3475 May Benefit Patients with NSCLC
A new experimental agent called MK-3475 already has shown dramatic promise for treating patients with melanoma; now it is showing early potential as an effective treatment for patients with NSCLC. MK-3475 is an anti-programmed cell death protein 1 (anti-PD-1) designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein.
The preliminary results of a phase 1B study from a cohort of 38 previously treated patients with NSCLC who received MK-3475 showed a response rate of 24%.2 Among the patients who responded, the median response duration had not been reached at the time of analysis (more than 62 weeks).2
In this study, all patients received MK-3475 every 3 weeks. The most commonly reported drug-related adverse effects were rash, pruritus, fatigue, diarrhea, and joint pain. However, one case of a drug-related grade 3 pulmonary edema was reported.
“The response rate that we have seen exceeded what would have been anticipated in this cohort. All 38 patients had received two lines of systemic therapy and that is where we see a lot of failures,” said study investigator Edward Garon, MD, Director of Thoracic Oncology at UCLA’s Jonsson Comprehensive Cancer Center, Los Angeles, CA, in an interview with ChemotherapyAdvisor.com. “It is certainly a promising agent.”
“We certainly still have a long way to go in lung cancer, but there have been many advances and the targeted therapies that have made a difference,” Dr. Garon added. “This drug and this class of agents may be able to help make a greater impact.”
- Csiki I, Simone CB, Heskel M, et al. Metformin as a radiosensitizer for lung cancer Presented at the International Association for the Study of Lung Cancer 15th World Conference on Lung Cancer; October 27-30, 2013; Sydney, Australia. Abstract MO05.10.
- Garon EB, Balmanoukian A, Hamid O, et al. Preliminary clinical safety and activity of MK-3475 monotherapy for the treatment of previously treated patients with non-small cell lung cancer (NSCLC) Presented at the International Association for the Study of Lung Cancer 15th World Conference on Lung Cancer; October 27-30, 2013; Sydney, Australia. Abstract MO18.02.Australia.