Mark G. Kris, MD
Although targeted therapy and immunotherapy have been well validated, chemotherapy has been and will remain integral to the treatment of patients with non–small cell lung cancer (NSCLC), says Mark G. Kris, MD.
“There's no targeted therapy, no antiangiogenesis therapy, no immune checkpoint blocker that has been shown to improve the chance of cure,” said Kris. “Of all the systemic therapies we have to fight lung cancers, only cytotoxic chemotherapy—particular cisplatin-based chemotherapy—has been shown to improve the chance of cure.”
Ongoing clinical trials are now looking to consolidate the benefits of chemotherapy and targeted agents and/or immunotherapies in combination regimens, Kris explained. Emerging evidence has confirmed the progression-free survival (PFS) and overall survival (OS) benefit of combination chemotherapy and targeted agents.
For example, results of the phase III IMpower150 trial demonstrated that the combination of atezolizumab (Tecentriq), bevacizumab (Avastin), carboplatin, and paclitaxel delayed progression or death by 38% versus bevacizumab and chemotherapy alone for patients with advanced nonsquamous NSCLC. The median PFS was 8.3 months versus 6.8 months, respectively (HR, 0.62; 95% CI, 0.52-0.74; P
Genentech (Roche), the manufacturer of atezolizumab and bevacizumab, also reported in a press release in March 2018 that the atezolizumab combination had been shown to improve OS in the study, as well.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Advanced Non–Small Cell Lung Cancer, Kris, William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center, discussed the continued significance of chemotherapy in patients with NSCLC in the era of targeted agents and immunotherapy.
OncLive: Please provide an overview of your presentation.
My topic of discussion tonight is the use of chemotherapy. By chemotherapy, I mean drugs that target the cell cycle. There is a misconception that chemotherapy is not a targeted treatment, but it actually is. We're not quite as sure about the target as we are perhaps with EGFR tyrosine kinase inhibitors (TKIs), but we know how it works. Chemotherapy does affect cells, particularly cells that have already undergone a neoplastic transformation. Chemotherapy given with radiation, or given before or after surgery can improve the chance of cure. It's really the only treatment today that can do that.
The other extraordinary thing is the emergence of more data showing that giving more targeted agents with cell cycle–targeted chemotherapies improves outcomes above those targeted immune or antiangiogenic therapies. The first example of that would be with bevacizumab. Bevacizumab and now ramucirumab (Cyramza) given with chemotherapy has been shown to improve outcomes over those agents alone. There is much excitement surrounding the recent data on bevacizumab in combination with cell cycle–targeted chemotherapy and atezolizumab.
The other area that is exploding is the use of checkpoint inhibitors. The drugs that physicians now have include pembrolizumab (Keytruda), atezolizumab, nivolumab (Opdivo), and durvalumab (Imfinzi). There’s emerging evidence that when you give drugs with chemotherapy, there are improved outcomes both in terms of PFS and OS. It is going to give a new life to chemotherapy. Giving chemotherapy with checkpoint inhibitors will become the standard of care in virtually every patient with NSCLC. For those who get chemotherapy and then suffer disease progression, a checkpoint inhibitor can be helpful.
The other interesting area is targeted therapies. Any guideline for the treatment of patients with an EGFR-targeted therapy, for example, states that patients who progress on an EGFR TKI require a change in systemic therapy. Chemotherapy is the universal treatment that is both helpful and recommended in the guidelines.
The interesting thing about patients who have an oncogenic target is that giving a chemotherapy drug is more effective than in patients without a target. The 2 clearest examples of that are the use of pemetrexed in patients with ALK
-positive NSCLC. There's a randomized trial comparing chemotherapy with crizotinib (Xalkori). In that trial, crizotinib beat chemotherapy in terms of PFS, but the response rates of chemotherapy in ALK
-positive patients were much better than you would expect. Pemetrexed was better than docetaxel. The IPASS trial led to the widespread use of upfront gefitinib (Iressa) after showing that response rates with chemotherapy in patients with EGFR
mutations were double that of patients without mutations.