LUNG CANCER

Five-year clinical outcomes after neoadjuvant nivolumab in resectable non-small cell lung cancer

A recent study demonstrated that neoadjuvant nivolumab led to improved 5-year recurrence-free and overall survival rates compared with historical outcomes among patients with resectable non-small cell lung cancer (Clin Cancer Res 2023; https://doi.org/10.1158/1078-0432.CCR-22-2994). Initial findings from this Phase I/II trial found this treatment approach to be safe and feasible with encouraging major pathological responses (MPR). The study authors are now reporting 5-year clinical outcomes from this trial, which they noted is the longest follow-up data for neoadjuvant anti-PD-1 in any cancer type. Twenty-one patients with Stage I-IIIA NSCLC were given two doses of nivolumab (3 mg/kg) for 4 weeks before surgery. The objectives of this study were to evaluate 5-year recurrence-free survival (RFS), overall survival (OS), and associations with MPR and PD-L1. For patients who had surgical resection, 60 percent were recurrence-free 5 years post-surgery and 80 percent were alive. These patients surpassed the 36-68 percent 5-year survival rate historically observed in patients having Stage I-III NSCLC, according to the study authors.

"The presence of MPR and pre-treatment tumor PD-L1 positivity (TPS >=1%) each trended toward favorable RFS; HR of 0.61 [95% CI: 0.15-2.44] and HR of 0.36 (95% CI: 0.07-1.85), respectively," the investigators wrote. "At 5-year follow-up, eight of nine (89%) patients with MPR were alive and disease-free." They observed no cancer-related deaths among patients with MPR. Six of the 11 patients without MPR experienced tumor relapse and three died. The study authors acknowledged this research is limited by the cohort size and ongoing, larger-scale studies are needed. However, the results highlighted that neoadjuvant nivolumab monotherapy in NSCLC provided good long-term clinical outcomes with low toxicity, and "clinicians should be confident in using immune checkpoint blockade in the pre-operative setting."

AUTHOR COMMENTARY: "The results from the 5-year follow-up analysis indicate that neoadjuvant nivolumab was safe in long-term follow-up and led to encouraging survival in this patient cohort," said senior author, Patrick Forde, MBBCh, Associate Professor of Oncology and Director of the Thoracic Oncology Clinical Research Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, in a statement. "The long-term safety and efficacy data from this study provide further support for the use of nivolumab in the neoadjuvant setting."

MELANOMA

Neoadjuvant-adjuvant or adjuvant-only pembrolizumab in advanced melanoma

For individuals having resectable Stage III or IV melanoma and receiving pembrolizumab before and after surgery, event-free survival was found to last longer in comparison to patients receiving adjuvant pembrolizumab alone. These findings, which also revealed no new toxic effects, were published in the New England Journal of Medicine (2023; doi: 10.1056/NEJMoa2211437). The study authors enrolled 345 participants having Stage IIIB to Stage IV melanoma found to be operable. Participants ages 18-90 were randomized to receive either upfront surgery followed by 200 mg of pembrolizumab every 3 weeks (adjuvant only) for a total of 18 doses, or 200 mg of pembrolizumab every 3 weeks for three doses leading up to surgery (neoadjuvant-adjuvant), then an additional 15 doses following surgery, according to the investigators. The primary endpoint was event-free survival in the intention-to-treat population. At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) experienced longer event-free survival versus the adjuvant-only group (159 patients). The researchers saw consistent benefit with neoadjuvant therapy across a range of factors, including patient age, sex, performance status, and stage of disease. Safety analysis showed that adverse events were similar in both arms of the study. Treatment-related adverse events of Grades 3 or higher during therapy were 12 percent in the neoadjuvant-adjuvant group and 14 percent in the adjuvant-only group.

AUTHOR COMMENTARY: "It's not just what you give, it's when you give it. The S1801 study demonstrates the same treatment for resectable melanoma given before surgery can generate better outcomes," noted Sapna Patel, MD, Chair of the SWOG Melanoma Committee and Associate Professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center. "In this case, we used the immune checkpoint inhibitor pembrolizumab. This treatment relies on the presence of pre-existing T cells coming in contact with cancer cells in the body to generate an immune response, and we found that starting treatment before the melanoma is removed-and with it the bulk of tumor-specific T cells-leads to a greater response than giving it after surgery.

"Based on the findings from S1801, patients with high-risk melanoma should start immunotherapy prior to surgery to generate an immune response while the bulk of the melanoma and the anti-tumor T cells are intact," she concluded. "Future studies can explore de-escalation strategies for both surgery and adjuvant therapy, as well as approaches for patients whose melanoma does not respond to neoadjuvant therapy."

VAPING

Not all vaping is the same: Differential pulmonary effects of vaping cannabidiol versus nicotine

A study from Roswell Park Comprehensive Cancer Center suggests that vaping cannabidiol (CBD)-a compound found in marijuana-leads to more severe lung damage than vaping nicotine (Thorax 2023; doi: 10.1136/thorax-2022-218743). This preclinical research effort involved both in vivo models and in vitro cultures of human cells, which were exposed to filtered air, nicotine aerosols, or CBD aerosols for 2 weeks. The researchers also found that the number and severity of focal lesions in the lungs were greater after inhalation of CBD aerosols than nicotine aerosols. The data showed that myeloperoxidase activity was significantly greater following exposure to CBD aerosol versus nicotine aerosol. Inhalation of CBD aerosols resulted in greater inflammatory changes and higher oxidative stress in the lung, and the study authors also reported that exposure to CBD aerosols killed purified human neutrophils at a higher rate than nicotine aerosols (44.5% vs. 21%). This work emphasizes how important it is for health care providers to focus on the specifics of a patient's smoking history, according to study author Yasmin Thanavala, PhD, in the Department of Immunology at Roswell Park. The study authors noted further research needs to investigate the long-term effects in people who regularly vape CBD and nicotine. Studies should also evaluate the effects of vaping products that contain other types of cannabinoids, including tetrahydrocannabinol.

AUTHOR COMMENTARY: "Our findings suggest that vaping cannabis may not only cause significant lung injury, but can also increase susceptibility to respiratory infections, lead to poor responses to prophylactic vaccinations, or cause worsening of symptoms in patients with underlying pulmonary inflammatory disease," Thanavala noted. "So, it's not enough for care providers to ask people, 'Do you smoke?' The next step is, 'Do you vape?' If the answer is yes, you need to ask, 'Do you vape nicotine or do you vape cannabis?' While cannabis has proven health benefits in pain management, sleep, relieving the symptoms of chemotherapy-induced nausea/vomiting in cancer patients, and in patients experiencing seizures, there is simply a lack of robust evidence about cannabis safety when delivered from vaping products," emphasized Thanavala and colleagues.