ASCO 2023 Abstract - Lung Cancer Immunotherapy Update

The following article is transferred from Xiamen Spacegen.Co.,Ltd （SpaceGen cancer research newsletter）

The 59th Annual Meeting of the American Society of Clinical Oncology (ASCO) will be held in Chicago, United States from June 2nd to 6th. On May 25, 2023, ASCO's official website released some abstracts of this conference. In this issue, we will explore the new developments in lung cancer immunotherapy presented at the ASCO conference.

Pembrolizumab and ramucirumab as neoadjuvant therapy for PD-L1-positive stage IB-IIIA lung cancer (EAST ENERGY).

Abstract Number: 8509

Title: Pembrolizumab and ramucirumab neoadjuvant therapy for PD-L1-positive stage IB-IIIA lung cancer (EAST ENERGY).

Clinical trial information: NCT04040361

Background: Neoadjuvant therapy with novel combination regimens is being developed for resectable non-small cell lung cancer (NSCLC). It has been reported that anti-angiogenic agents can modulate tumor immunity, and the efficacy and safety of adding immune checkpoint inhibitors (ICI) therapy have been studied in advanced NSCLC. In this multicenter phase II study, researchers evaluated the efficacy and feasibility of neoadjuvant therapy with pembrolizumab and ramucirumab (a direct vascular endothelial growth factor receptor-2 antagonist) in PD-L1-positive, clinically staged IB-IIIA NSCLC patients followed by surgery.

Inclusion criteria: Pathologically confirmed NSCLC patients (age ≥ 20 years) with PD-L1 expression ≥ 1% (22C3), resectable clinical stage IB-IIIA NSCLC, and performance status of 0-1. Patients received two cycles of pembrolizumab (200mg per individual) and ramucirumab (10mg/kg) treatment every three weeks. Surgery was planned 4-8 weeks after the last dose. The primary endpoint was to determine the major pathological response (MPR) rate. The sample size was calculated based on the exact binomial distribution, considering a threshold MPR rate of 20%, an expected MPR rate of 45%, one-sided α of 5%, and an anticipated power of 80%.

Results: Between July 2019 and April 2022, a total of 24 eligible patients were enrolled, with a median age of 75 years (range: 50-78 years); 18 patients were male. Histological subtypes included adenocarcinoma in 12 cases, and clinical staging was IB, IIA, IIB, and IIIA in 1, 4, 9, and 10 cases, respectively. Nine patients (37.5%) had PD-L1 expression ≥ 50%. The major pathological response (MPR) rate assessed by a central independent review committee (BICR) consisting of three pathologists was 50.0% (90% CI, 31.9%-68.1%), thus meeting the primary endpoint. Among the 12 patients who achieved MPR, 6 of them showed pathological complete response. One patient experienced pneumonia before neoadjuvant therapy, and one patient showed disease progression after neoadjuvant therapy. During the course of treatment, grade 3 adverse events (AEs) occurred in 9 out of 24 patients (37.5%). Three patients had postoperative complications associated with grade 3 AEs, including postoperative hematoma, lung fistula, and intraoperative arterial injury. Immune-related AEs associated with the treatment regimen included thyroid dysfunction (3 cases), acute interstitial nephritis (2 cases), and hepatic dysfunction (2 cases); however, no grade 3 or higher AEs were observed. Twenty-one patients achieved R0 resection, and one patient underwent R1 resection. Notably, there were no significant wound healing complications attributable to the anti-VEGF effects of ramucirumab.

Conclusion: The results of this study demonstrate that this novel combination of immune checkpoint inhibitors (pembrolizumab) and anti-VEGF agents (ramucirumab) as neoadjuvant therapy is feasible and shows encouraging results.

SWOG S1929 Study: Phase II Randomized Study of Atezolizumab vs. Atezolizumab plus Talazoparib Maintenance Therapy in SLFN11-Positive Extensive-Stage Small Cell Lung Cancer Patients.

Abstract Number: 8504

Title: SWOG S1929: Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer (ES-SCLC).

Clinical Trial Information: NCT04334941

Background: The addition of immune checkpoint inhibitors (ICI) to chemotherapy has shown moderate improvement in overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). A retrospective analysis of SCLC patients treated with a combination of PARP inhibitors (PARPi) and temozolomide showed that SLFN11-positive expression predicted a benefit in progression-free survival (PFS) and OS. This study aims to evaluate whether the addition of PARPi to standard maintenance ICI (atezolizumab) improves the prognosis of SLFN11-positive ES-SCLC patients after first-line chemotherapy and immune therapy.

Inclusion Criteria: The study includes patients with extensive-stage small cell lung cancer who are SLFN11-positive (immunohistochemistry H-score ≥ 1) and have not progressed after frontline treatment. Patients were randomized in a 1:1 ratio to receive either atezolizumab (T) or atezolizumab plus talazoparib (AT). Stratification was based on performance status (PS) score and whether the patient received thoracic radiation therapy. The primary endpoint is PFS, and secondary endpoints include overall response rate (ORR), OS, and safety. The primary endpoint is tested at a one-sided 10% significance level.

Results: A total of 106 patients were randomized, with a median follow-up of 5 months. The median age of patients was 67 years (range: 45-84 years), 48% were female, and 89% were White. 96% of patients had a PS score of 0-1, and 25% of patients received radiation therapy. PFS events were reported in 80 patients, with median PFS of 2.8 months in the atezolizumab group and 4.2 months in the atezolizumab plus talazoparib group (HR=0.70, 80% CI: 0.52-0.94, p=0.056). The median OS was 8.5 months in the atezolizumab group and 9.4 months in the atezolizumab plus talazoparib group. The ORR was 16% in the atezolizumab group and 12% in the atezolizumab plus talazoparib group. Grade 3 or higher non-hematologic treatment-related adverse events occurred in 13% and 15% of patients, respectively, and the incidence of hematologic adverse events was 4% and 50%, respectively. No grade 5 treatment-related adverse events were reported. One patient experienced grade 3 febrile neutropenia. The incidence of grade 3 or higher anemia was 2% in the atezolizumab group and 37% in the atezolizumab plus talazoparib group. Three patients discontinued treatment due to safety concerns.

Conclusion: The study achieved its primary endpoint, indicating that maintenance AT therapy improves PFS in SLFN11-positive ES-SCLC patients. As expected, AT was associated with increased hematologic toxicity, mostly grade 3 anemia. This study demonstrates the feasibility of conducting biomarker-driven trials in SCLC and paves the way for evaluating new treatment approaches in selected SCLC populations in the future.

NEOpredict-Lung study: Latest results of 4-year follow-up on PD-1 combined with LAG3 antibody neoadjuvant therapy have been released.

Abstract number: 8500

Original title: Surgical outcomes of patients with resectable non-small-cell lung cancer receiving neoadjuvant immunotherapy with nivolumab plus relatlimab or nivolumab: Findings from the prospective, randomized, multicentric phase II study NEOpredict-Lung.

Clinical trial information: NCT04205552.

Background: The feasibility of surgical resection following neoadjuvant immune checkpoint inhibitor therapy (PICIT) with PD-1 and CTLA-4 inhibitors has been established in non-small-cell lung cancer (NSCLC). This study reports, for the first time, data on surgical outcomes in NSCLC patients undergoing neoadjuvant treatment with a LAG-3 inhibitor.

Study design:

Inclusion criteria: Patients diagnosed with resectable NSCLC stages IB, II, or IIIA (UICC 8th edition) were randomized to receive two preoperative doses (every 14 days) of either nivolumab (240 mg, Group A) or nivolumab plus relatlimab (240 mg and 80 mg, respectively, Group B). The primary endpoint was the number of patients undergoing surgical resection within 43 days of starting PICIT. Surgery was performed according to institutional standards. Prospective recording of outcomes and perioperative events was conducted.

Results: From April 2020 to July 2022, a total of 60 patients (29 females) were enrolled and randomized in a 1:1 ratio. All patients underwent surgery within 43 days of starting PICIT. The median age in Group A was 65 years (range 43-78 years) and in Group B was 67 years (range 44-81 years). The clinical UICC stages were similar between the two groups. Central tumor location was observed in 50% of Group A and 45% of Group B. R0 resection was achieved in 57 patients (95% ITT population, 98.3% complete resection population). Only two patients had pleural carcinomatosis detected intraoperatively, and one patient underwent R1 resection. Surgical procedures included lobectomy (n=23 and 24), wedge resection (2 and 1), sleeve lobectomy (5 and 4), and combined lobectomy+segmentectomy (0 and 1). Surgical approach was thoracoscopic in 60% and 63.3%, and open surgery in 40% and 36.6% of cases. Conversion was required in 3 patients in Group A and 2 patients in Group B. The median operative time was 149 minutes (range 77-234 minutes) and 165 minutes (range 61-205 minutes). The median number of lymph nodes resected was 15 (range 3-52) and 10 (range 3-50). One patient in each group experienced pulmonary artery bleeding intraoperatively, which was successfully managed without sequelae. Postoperative complications occurred in 33.3% and 26.6% of patients, respectively. The mean hospital stay was 7 days (range 2-22 days) in Group A and 5.5 days (range 2-24 days) in Group B. Complete or major pathological response was observed in 27% and 30% of patients, respectively. The overall 30-day perioperative mortality rate was 0%. No negative impact on adjuvant therapy was observed. The 12-month overall survival rates were 96% (95% CI: 83-99%) in both groups, and the disease-free survival rates were 91% (95% CI: 78-97%).

Conclusion: Radical surgical resection following neoadjuvant treatment with PD-1/LAG-3 inhibition is equally safe and feasible compared to PD-1 inhibition alone. Perioperative course, complication rates, and prognosis are comparable to other neoadjuvant treatment regimens. Standard adjuvant therapy is safe in this context.

Reference

[1] Pembrolizumab and ramucirumab neoadjuvant therapy for PD-L1-positive stage IB-IIIA lung cancer (EAST ENERGY)

[2] SWOG S1929: Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer (ES-SCLC).

[3] Surgical outcomes of patients with resectable non-small-cell lung cancer receiving neoadjuvant immunotherapy with nivolumab plus relatlimab or nivolumab: Findings from the prospective, randomized, multicentric phase II study NEOpredict-Lung.