During a recent PW Podcast episode, we spoke with Patrick Forde, MBBCh, Director of the Thoracic Can- cer Clinical Research Program and Associate Professor of Oncology at Sidney Kimmel Comprehensive Cancer Center and Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University, about the results of the phase III CheckMate 816 trial, which investigated nivolumab platinum-doublet chemother- apy versus chemotherapy alone as neoadjuvant treat- ment for resectable (IB-IIIA) non-small cell lung cancer (NSCLC). Following is a summary of that interview:
What makes the CheckMate 816 study particularly interesting for oncologists?
We know that, historically, patients with newly diagnosed stage I-III NSCLC have a high rate (45% to 70%) of relapse after surgery for their lung cancer. And when it does relapse, it’s usually incurable. This study compared immunotherapy with nivolumab along with chemotherapy prior to surgery to chemotherapy alone in this patient population.
Patients who receive chemotherapy prior to sur- gery for lung cancer usually have a very low rate of pathologic complete response (PCR), meaning lack of any residual viable cancer in the specimen at the time of resection, which historically occurs in about 2% to 10% of patients. The addition of nivolumab to chemotherapy increased the PCR rates from 2.2% with chemotherapy alone to 24.0%. We also showed that there was a signifi- cant reduction in the amount of viable tumor at the time of surgery, from 74% with chemother- apy alone to only 10% with chemotherapy plus nivolumab. Also, the addition of nivolumab to chemotherapy prior to surgery did not impair the surgery in any way. More patients actually went to surgery in the chemotherapy plus nivolumab arm of the study, and there were very similar rates of toxicity, so the combination didn’t appear to add side effects to chemotherapy.
When we looked at multiple subgroups of patients, the benefit of adding nivolumab to chemotherapy seemed to be sustained across all analyzed subtypes, including histology (squamous vs non-squamous), PD-L1 status (positive vs negative, and tumor mu- tation burden. There wasn’t a specific subgroup who were selected out as most likely to benefit.
In general, the study population was representative of typical patients with NSCLC. About 20% to 30% of patients would have stage I or II disease when diagnosed, and another approximately 20% would have stage III disease. With the advent of lung cancer screening, we’re seeing more and more patients with these earlier stages of disease, which improves the chances of cure by detecting them earlier. However, with many patients experiencing relapse after surgery, we’re trying to improve that by bringing immunotherapy into early-stage disease.
We’re also following participants in both arms for event-free survival, essentially looking for any events, such as patients not going to surgery, hav- ing relapse of their cancer, or cancer-related mor- tality. In the longer-term, when we have the event- free and overall survival data, it will be useful to correlate that with PCR, hopefully allowing use to broaden the use of PCR as an endpoint.
To listen to our full PW Podcast interview with Dr. Forde, visit www.physiciansweekly.com/forde or scan the QR code at left.