Sintilimab plus anlotinib as second‐ or third‐line therapy in metastatic non‐small cell lung cancer with uncommon epidermal growth factor receptor mutations: A prospective, single‐arm, phase II trial

Abstract

BackgroundPatients with non‐small‐cell lung cancer (NSCLC) and uncommon EGFR alterations typically have worse treatment outcomes than patients with classically EGFR‐mutated NSCLC. This study aimed to investigate the efficacy and safety of PD‐1 blockade with sintilimab plus anti‐angiogenic treatment with anlotinib in patients with NSCLC harboring uncommon EGFR mutations.MethodsPatients with metastatic NSCLC harboring uncommon EGFR mutations after two previous treatments, including a platinum‐based chemotherapy regimen and a targeted treatment (or chemotherapy only for patients harboring EGFR ex20ins), received sintilimab combined with anlotinib. The primary endpoint was objective response rate (ORR).ResultsAt data cutoff (September 27, 2022), median follow‐up was 22.3 months (range, 1.2–37.6). Among 21 enrolled patients, 12 had EGFR ex20ins and nine had other uncommon EGFR mutations such as L861Q, G719A, and G709X. Overall, eight patients (38.1%) achieved an objective response, and 18 (85.7%) achieved disease control. Median (95% CI) progression‐free survival (PFS) was 7.0 (5.4–8.6) months, and median overall survival (OS) was 20.0 (15.6–24.4) months. The 12‐month PFS rate (95% CI) was 22.2% (7.4–42.0), and the 12‐month OS rate was 66.7% (42.5–82.5). Patients harboring EGFR ex20ins had similar ORR and PFS to those with other mutations. Six patients (28.6%) experienced grade 3 treatment‐related adverse events (TRAEs); hand‐foot syndrome was the most common grade 3 TRAE (2 patients; 9.5%). No grade ≥4 TRAEs were observed.ConclusionsThe combination of sintilimab and anlotinib demonstrated durable efficacy and was generally well tolerated in patients with NSCLC and uncommon EGFR mutations who had received prior standard‐of‐care treatments. (ClinicalTrials.gov identifier: NCT04790409).

Case report: Sintilimab combined with anlotinib as neoadjuvant chemotherapy for metastatic bone tumor resection in patients with PSC

“…Sintilimab is a novel highly selective humanized IgG4 monoclonal antibody that blocks the interaction between PD-1 and its ligand by binding site of programmed cell death PD-1, thereby restoring the function of endogenous T cell and eliminating tumor cells ( 3 , 6 ). It has been proven to have encouraging antitumor activity and clinically beneficial in the treatment of advanced solid tumors including advanced NSCLC ( 13 , 14 ).…”

“…It helps tumor cells evade immune surveillance and ultimately leads to an immunosuppressive tumor microenvironment ( 3 , 16 ). As a novel multitarget antiangiogenic drug, anlotinib is currently approved as a third-line treatment of NSCLC by the National Medical Products Administration (NMPA) ( 3 , 14 ). It can down-regulate the expression of PD-L1 on vascular endothelial cells, reducing hypoxia, increasing CD8+ T cell infiltration, inhibiting recruitment of tumor-associated macrophages and enhancing the immune surveillance on tumor cells, thereby inhibiting the tumor ( 14 ).…”

“…A growing amount of evidence describes the significantly synergistic therapeutic benefits against a variety of tumors between sintilimab and anlotinib ( 3 , 11 , 14 , 17 ). Antiangiogenic agents plus PD-1 inhibitors showed promising activity in patients with advanced soft tissue sarcoma (STS) ( 18 ).…”

The current landscape, advancements, and prospects in the treatment of patients with EGFR exon 20 insertion mutations warrant scientific elucidation

“…These results prompt a reconsideration of treatment strategies, akin to the clinical trials Impower 130 ( 52 ) and Impower 150 ( 53 ), where the combination of chemotherapy, immunotherapy, and anti-angiogenesis agents demonstrated potential benefits. In a prospective, single-arm, phase II trial ( 51 ) ( Table 3 ), the efficacy and safety of the combination of sintilimab and anlotinib were investigated in rare EGFR-mutated NSCLC patients who had previously received second-line therapy. The results were based on a cohort of 21 patients, comprising 12 with EGFR exon 20 insertions and 8 with other rare mutations.…”

Immune checkpoint inhibitors: breakthroughs in cancer treatment

“…After a long follow-up period, the KEYNOTE-426 clinical study has demonstrated that treating untreated advanced RCC with a combination of pembrolizumab and axitinib is beneficial for patients. In the recently conducted clinical trial NCT0479040926 29 , sintiliumab, the second domestically developed PD-1 inhibitor approved in China, in combination with the anti-angiogenesis agent anlotinib, has shown remarkable results. The combination therapy achieved a superior overall response rate to those of chemotherapy and monotherapy with either agent alone.…”