KEY TAKEAWAYS
- This phase I study evaluated the safety and efficacy of adding SBRT to ipi/nivo in first-line metastatic NSCLC.
- Multisite SBRT combined with dual checkpoint immunotherapy showed promising results and good tolerance as a first-line treatment for metastatic NSCLC.
The Checkmate 227 trial identified the combination of ipilimumab and nivolumab (ipi/nivo) as a viable first-line treatment for stage IV non-small cell lung cancer (NSCLC), with a median overall survival of 17.1 months. Stereotactic Body Radiotherapy (SBRT) offers strong control over metastasis and could synergize with immunotherapy by offering direct cytoreduction and preventing early site-specific progression, thereby enhancing long-term results. A phase I study was thus formulated to assess the safety and efficacy of combining SBRT with ipi/nivo in the first-line management of metastatic NSCLC.
Newly diagnosed patients (pts) with ECOG scores of 0-1 underwent SBRT targeting 1 to 4 isocenters. Not all metastatic lesions were addressed, and those larger than 65 cc were partially irradiated. Brain metastases greater than 3mm were treated before enrollment. SBRT doses were site-dependent, ranging from 30 to 50 Gy delivered in 3 to 5 fractions. The first cycle of ipi/nivo was administered either concurrently with SBRT or up to one week afterward. Immunotherapy could continue for up to two years or until disease progression, with treatment beyond progression being allowed based on clinical judgment.
Out of 97 screened individuals, 75 were enrolled and underwent SBRT along with at least one cycle of immunotherapy (average age 65; 55% male, 45% female). Histological classifications included adenocarcinoma (73%), squamous cell carcinoma (17%), and other types of NSCLC (9%). Four pts (5.3%) experienced dose-limiting toxicity, all grade 3 pneumonitis. PD-L1 expression levels were varied: 46.7% had 0%, 32% had 1-49%, 18.7% had ≥50%, and 2.7% were unknown. Brain metastases were found in 32%, and liver metastases in 16%.
On the first imaging follow-up, 72 pts were assessed: 4 had a complete response (5.6%), 35 had a partial response (48.6%), 9 had stable disease (12.5%), and 24 showed disease progression (33.3%). The objective response rate was 54.2%, and the disease control rate was 66.7%. Median progression-free survival (PFS) was 5.7 months, while overall survival (OS) was 34 months. PFS was not significantly influenced by the presence of liver or brain metastases but was higher in those with PD-L1 levels of ≥1% (p=0.008).
The combined approach of multisite SBRT and dual checkpoint immunotherapy was generally well-tolerated for first-line treatment in advanced NSCLC. The median OS was 34 months in a cohort with a high percentage of negative PD-L1 expression, suggesting promising results and justifying further study. Future prospective study involving radiomic and plasma correlative analysis is planned for patient selection.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/950
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03223155
Juloori, A., Bestvina, C.M., Pointer, K.B., Pitroda, S.P., Abazeed, M.E., Katipally, R.R., Sivananthan, A.P., Hoffman, P.C., Mohammed, T., Rayani, S., Rampurwala, M., Narula, S., Garassino, M.C., Weichselbaum, R.R., Vokes, E.E., Patel, J.D., Chmura, S.J. The Addition of Multisite SBRT to Ipilimumab and Nivolumab in First Line Metastatic NSCLC: The COSINR Trial.
