Safety and Tolerability Evaluation of Sintilimab in Combination with Low Dose Radiation and SBRT in Treatment Naive Stage IV PD-L1 Positive NSCLC Patients

Abstract

The number of pulmonary nodules identified incidentally or through lung cancer screening programs has dramatically increased. The role of radiation therapy (RT) in this patient population is not defined. Our institution established a multidisciplinary Pulmonary Nodule and Lung Cancer Screening Clinic (PNLCSC) to optimize the management of these patients. In this study, we describe the role of radiation oncologists in the multidisciplinary evaluation and management of incidental and screening-identified pulmonary nodules. Materials/Methods: This study included patients referred to the PNLCSC between 10/2012 and 9/2019. Indications for referral included a Lung-RADS 4 finding on screening CT or an incidental pulmonary nodule measuring 6 mm. At each clinic session, a multidisciplinary team including diagnostic/interventional radiologists, pulmonologists, medical oncologists, thoracic surgeons, and radiation oncologists made recommendations regarding the work-up, management, and follow-up of each patient. Demographic and clinical characteristics as well as data on followup and treatments were prospectively recorded. Collection and analysis of the data was approved by institutional IRB. Results: Of 1,150 patients evaluated by the PNLCSC, 234 (20.3%) were screening patients, and 916 (79.7%) had incidental nodules. Among screening patients, 41 (17.5%) underwent therapeutic intervention, 31 (13.2%) with surgical resection and 10 (4.3%) with RT. RT represented 24.4% of all treatments received by screening patients. Among patients with incidental pulmonary nodules, 227 underwent therapeutic intervention, with 167 (18.2%) and 60 (6.6%) receiving surgery and RT, respectively. The overall rate of patients undergoing RT was stable over time, ranging from 6.

Low‐dose radiation therapy mobilizes antitumor immunity: New findings and future perspectives

“…No grade 3 or above treatment-related toxicity was observed, and the incidence of grade 2 or above radiation-related pneumonitis and immune-related pneumonitis was <10% in a prospective clinical trial. 149 No LDRT-related adverse effect (AE) was reported in another small-sample phase I clinical trial. 87 Data from a phase II clinical study showed no significant difference in the incidence of dose-limiting toxicity between the combined LDRT and non-combined LDRT group.…”

“…Another important issue is the frequency of administration. The relatively traditional RT mode adopted one-time RT (once or several fractions in succession), 81,143,149 RT (periodic administration) was believed to rescue the decline of immune cells over time after LDRT. 87,150,151 There are no evidencebased recommendations for the best immunotherapeutic drug combined with LDRT.…”

Sintilimab for the treatment of non-small cell lung cancer

“…In the dose escalation phase of a phase I study (NCT03812549), the synergistic anti-tumor effect of LDRT combined with sintilimab following SBRT was explored in 12 stage IV NSCLC patients, with primary endpoints of safety and tolerability [ 53 ]. The combination plan showed no dose-limiting toxicities, with no grade 3 or higher AEs, while the ORR among 10 evaluable patients was 70% [ 53 ].…”

“…In the dose escalation phase of a phase I study (NCT03812549), the synergistic anti-tumor effect of LDRT combined with sintilimab following SBRT was explored in 12 stage IV NSCLC patients, with primary endpoints of safety and tolerability [ 53 ]. The combination plan showed no dose-limiting toxicities, with no grade 3 or higher AEs, while the ORR among 10 evaluable patients was 70% [ 53 ]. Interestingly, the combination therapy increased the number of T cell clones and TCR diversity, and decreased the PD-1 expression on CD8 + T cells and circulating tumor DNA (ctDNA) in the patients’ peripheral blood samples [ 53 ].…”

“…The combination plan showed no dose-limiting toxicities, with no grade 3 or higher AEs, while the ORR among 10 evaluable patients was 70% [ 53 ]. Interestingly, the combination therapy increased the number of T cell clones and TCR diversity, and decreased the PD-1 expression on CD8 + T cells and circulating tumor DNA (ctDNA) in the patients’ peripheral blood samples [ 53 ]. With an acceptable safety profile, sintilimab plus radiation therapy is undergoing several clinical trials in lung cancer patients [ 54 ].…”