P1.18-06 Efficacy and Safety of Neoadjuvant PD-1 Blockade with Sintilimab in Resectable Non-Small Cell Lung Cancer

Abstract

Background: Ceritinib is a highly selective ALK inhibitor that has been shown potent antitumor activity against ALK-positive nonsmall cell lung cancer (NSCLC). We conducted a multicenter singlearm phase II study to assess the efficacy and safety of neoadjuvant therapy with ceritinib followed by surgery in patients with ALKpositive resectable locally advanced (LA) NSCLC. Method: Three cycles of ceritinib were administered as induction therapy. The drug was administered orally at the dose 750 mg once daily for 28 days per cycle. The primary endpoint was the major pathological response rate (mpRR). This study required 19 patients, with mpRR of 15% considered non-promising and 45% promising (one-side alpha ¼ 0.025; beta ¼ 0.2). Biomarker analyses using pre-and postceritinib through next-generation sequencing (NGS) of plasma and tissue is also planned. (Trial Identifier, UMIN000017906). Result: A total of 395 patients with LA-NSCLC were screened from March 2015 to March 2018 and 15 patients (4%) were identified as ALKpositive. Only 7 patients were enrolled because of slow accrual. The median age of the patients was 50 years and 71% (n¼5) were male. All patients had stage IIIA disease and adenocarcinoma. 6 out of 7 patients completed three cycles of neoadjuvant therapy with ceritinib as planned, 71% (n¼5) of patients required dose adjustment. One patient was withdrawn from the study because of hepatitis. The objective clinical response rate was 100%. Surgical resection was performed in 6 patients, and complete (R0) resection was achieved in 5 patients. Among the 7 evaluable patients, the mpRR was 57% (95% CI, 18 to 90); 4 patients achieved mpR and 2 patients achieved pathologic complete response. With a median follow-up of 10 (range 8-33) months, 1 patient died of disease progression and 6 patients remain alive, including 4 patients who are recurrence-free. The most common toxicities were gastrointestinal toxicities. Conclusion: Our results showed that neoadjuvant ceritinib is safe and effective, with a high rate of pathologic response, in patients with ALK-positive resectable LA-NSCLC, although the limitation of the data interpretation due to small sample size.

Neoadjuvant and Adjuvant Immunotherapy: Opening New Horizons for Patients With Early-Stage Non-small Cell Lung Cancer

“…As a whole, sintilimab has shown good safety profiles in neoadjuvant therapy for resectable NCSLC. Another study by Li et al ( 16 ) also showed that neoadjuvant sintilimab treatment in NSCLC patients was well tolerated, with an MPR of 40.5% and a pCR of 16.2%. A decrease in TMU on PET–CT rather than a change in the sum of lesion diameters (SLD) was also identified as a predictor of pathological response to anti-programmed cell death-1 (PD-1) therapy in early-stage NSCLC in another study.…”

Development of Prognostic Nomogram Based on Immune Scores in Lung Adenocarcinoma Patients

“…Even if there is a relapse, it will obviously move backwards in time, and it can increase the 5-year survival rate by about 20% [32 ]. It was con rmed ~ as for surgically resectable non-small cell lung cancer, neoadjuvant immunotherapy, high safety does not affect surgery, and the pathological signi cant remission rate is 45%, and the 18-month relapse-free survival rate is 73% [33]. Studies have also shown that early non-small cell cancer administration of immune drugs to block multiple molecular tags can kill cancer cells with fewer side effects [34].…”

Development of a Prognostic Nomogram for Patients with Lung Adenocarcinoma in the Stages I, II, and III Based on Immune Scores

“…For LUAD patients with high immune scores before and after surgery, immunotherapy or combined immunotherapy based on precise gene sequencing can reduce the harm of radiotherapy and chemotherapy. 31 Studies reported that postoperative immunotherapy could generally reduce the local recurrence rate by about 30%, significantly reduce distant metastases, and increase the 5-year survival rate by about 20%. 32 Even if the tumor recurred, the recurrence time could be obviously delayed.…”

“…For LUAD patients with high immune scores before and after surgery, immunotherapy or combined immunotherapy based on precise gene sequencing can reduce the harm of radiotherapy and chemotherapy. 31 Studies reported that postoperative immunotherapy could generally reduce the local recurrence rate by about 30%, significantly reduce distant metastases, and increase the 5-year survival rate by 32 Even if the tumor recurred, the recurrence time could be obviously delayed. 32 It was confirmed that for treating the resectable non-small cell lung cancer, neoadjuvant immunotherapy was highly safe and did not affect surgery, with 45% of the pathologically significant remission rate and 73% of the 18-month recurrence-free survival rate.…”