ELCC 2022 Voice of China's domestic drugs shine!

The 2022 European Lung Cancer Conference (ELCC) was held from March 30 to April 2 local time.
A number of studies led by Chinese experts were selected for this event, among which immunotherapy was one of the key points of discussion among the experts
.

As a domestic immune checkpoint inhibitor, sintilimab has shown great success in many cancer types in recent years.
Lung cancer is also one of the important areas of drug exploration.
12 and so on have also made considerable achievements
.

At this meeting, a number of studies evaluating the efficacy and safety of sintilimab announced their preliminary or final results, many of which were a blockbuster study in which the overall survival (OS) of patients with advanced lung cancer exceeded 2 years.
The editing is done as follows
.

Breakthrough 2 years! The final OS data of the ORIENT-11 study is released.
Background The previous results of the ORIENT-11 study showed that compared with placebo + pemetrexed + platinum (PPP), the first-line treatment of sintilimab + pemetrexed + Platinum (SPP) significantly improves progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC)
.

At an interim analysis conducted on November 15, 2019, the study met its primary endpoint of PFS
.

An updated OS analysis showed a benefit in patient OS as well, and here the investigators report the patient's final OS performance
.

Methods: A total of 397 patients with untreated locally advanced or metastatic non-squamous NSCLC (AMnsqNSCLC) were included in the study, and all patients had no EGFR or ALK gene mutation
.

Patients were randomly assigned to SPP (n=266) or PPP (n=131), stratified by PD-L1 expression level, platinum-based chemotherapy regimen, and gender
.

Patients receive treatment until disease progression (PD) or intolerable toxicity for up to 24 months
.

Patients in the PPP group could be crossed over to receive sintilimab monotherapy after PD
.

The primary endpoint of the study was PFS by blinded independent radiology assessment (according to RECIST v1.
1)
.

The key secondary endpoint was patient OS, defined here as the time from randomization to death from any cause
.

At the data cutoff date of September 15, 2021, patients were followed for a median of 30.
8 months
.

There were 151 OS events in the SPP group, an incidence rate of 57%, and 92 OS events in the PPP group, an incidence rate of 70%
.

Among them, 47% of patients in the PPP group received sintilimab monotherapy after PD
.

The median OS (mOS) was 24.
2 months in the SPP group and 16.
8 months in the PPP group (HR 0.
65; 95% CI, 0.
50-0.
85)
.

The estimated 2-year OS rate was 50% in the SPP group and 32% in the PPP group
.

After adjustment for crossover effects, the OS benefit was more significant in the SPP group (HR 0.
52; 95% CI, 0.
38-0.
69)
.

The OS benefits of the prespecified subgroups were generally consistent with the OS benefits of the overall population, and the overall between-subgroup variability was within the expected range
.

CONCLUSIONS: The final OS analysis of ORIENT-11 showed that for AMnsqNSCLC patients without EGFR or ALK mutations, first-line treatment with SPP showed a higher OS benefit than PPP
.

Safety and tolerability analysis of sintilimab in Chinese patients with NSCLC in ORIENT-11 and ORIENT-12 studies BackgroundIn the randomized double-blind phase III studies ORIENT-11 and ORIENT-12, sintilimab has Chinese patients with NSCLC showed good curative effect
.

To further assess the safety of sintilimab, the investigators report pooled safety and tolerability data from two studies
.

Research Methods ORIENT-11 enrolled 397 patients with AMnsqNSCLC and randomly assigned them to sintilimab 200 mg + pemetrexed + platinum group or placebo + pemetrexed + platinum group according to the ratio of 2:1 , the treatment cycle is every 3 weeks
.

ORIENT-12 enrolled 357 patients with advanced or metastatic squamous NSCLC, and randomly assigned the patients to sintilimab 200 mg + gemcitabine + platinum group or placebo + gemcitabine + platinum group in a 1:1 ratio, treatment The cycle is every 3 weeks
.

We summarized treatment-related adverse events (TRAEs), immune-related TRAEs (ir-TRAEs), and the association of ir-TRAEs with efficacy and assessed safety by pooled analysis
.

RESULTS: Of the 754 patients, 445 were assigned to sintilimab and 309 were assigned to placebo.
Baseline characteristics of patients with and without ir-TRAE were not significantly different between the two groups
.

The incidence of TRAE was 85.
8% in the sintilimab group and 81.
6% in the placebo group, with relatively consistent rates
.

The incidence of ir-TRAEs in the sintilimab group was higher than in the placebo group (42.
5% in the sintilimab group vs 30.
7% in the placebo group), but the incidence of grade ≥ 3 ir-TRAEs was similar in the two groups (sintilimab).
6.
1% in the limumab group vs 4.
9% in the placebo group)
.

It is worth noting, however, that the incidence of ir-TRAEs of rash, hypothyroidism, and immune-mediated pneumonitis was higher in the sintilimab group
.

Rates of TRAE-related discontinuation events (6.
5% in the sintilimab group vs 4.
2% in the placebo group) and deaths (0.
9% in the sintilimab group vs 2.
3% in the placebo group) were similar in both groups
.

Exploratory analysis showed that in the sintilimab group, patients with ir-TRAE had better PFS and OS compared with patients without ir-TRAE (Table 1)
.

Table 1 Exploratory analysis between ir-TRAE and patient survival (click to enlarge) Study conclusions For Chinese NSCLC patients in ORIENT-11 and ORIENT-12, the toxicity of sintilimab combined with chemotherapy is tolerable and safe Sexuality is controllable, which is basically consistent with the performance of patients in the placebo group in the study
.

Sintilimab combined with anlotinib may be a new treatment option for patients with rare EGFR-mutant NSCLC Study Background Patients with NSCLC with rare EGFR mutations generally have poorer treatment benefits compared with patients with common EGFR mutations
.

This study aimed to investigate the efficacy and safety of PD-1/PD-L1 inhibitors and anti-angiogenic therapy in patients with EGFR-mutant NSCLC
.

Methods A total of 21 patients with NSCLC who developed rare EGFR mutations after prior therapy were included, regardless of the patient's EGFR exon 20 insertion (EGFR Ex20ins) performance, and the patients' prior therapy included platinum-based regimens and targeted therapy
.

Patients were treated with sintilimab (a PD-1 inhibitor) in combination with anlotinib (a multi-targeted antiangiogenic drug), with the primary endpoint being objective response rate (ORR)
.

Results were at data cutoff on January 11, 2022, with a median follow-up of 15.
2 months
.

A total of 12 patients harbored EGFR Ex20ins mutations, and the remaining 9 patients harbored other EGFR mutations, including L861Q, G719A, and G709T
.

The median PFS of patients with rare EGFR mutations was 6.
7 months (95% CI, 2.
4-11.
0), and the 6-month PFS rate was 52.
4%
.

Among the 19 patients evaluable for efficacy, the ORR was 36.
8% and the disease control rate (DCR) was 84.
2%
.

Notably, patients with EGFR Ex20ins showed similar ORR, DCR, and PFS to patients with other mutation types (ORR: 36.
4% vs 37.
5%, p=1.
00; DCR: 90.
9% vs 75.
0%, p=0.
348; PFS: 4.
3 months vs 7.
1 months, p=0.
327)
.

The most common grade ≥3 TRAEs were hypertension (4.
8%), immune-related pneumonitis (4.
8%), and hand-foot syndrome (9.
5%)
.

The study concluded that the use of sintilimab and anlotinib did not increase safety issues.
For NSCLC patients with rare EGFR mutations, the combination therapy of sintilimab and anlotinib has durable efficacy and good efficacy.
Tolerability, further studies are urgently needed to evaluate this new chemotherapy-free strategy
.

Reference 1.
Y.
Yang, Z.
Wang, J.
Fang, et al.
Final overall survival (OS) data of sintilimab plus pemetrexed (SPP) and platinum as first-line (1L) treatment for locally advanced or metastatic nonsquamous NSCLC (AMnsqNSCLC) in the phase III ORIENT-11 study.
ELCC 2022 4MO.
2.
G.
Gao, Y.
Zhao, J.
Zhou, et al.
Safety and tolerability of sintilimab (sint) combination therapy in patients with advanced or recurrent non -small cell lung cancer (NSCLC): Pooled safety analysis of ORIENT 11 and ORIENT 12 studies.
ELCC 2022 17P.
3.
K.
Chen, Y.
Fan.
Sintilimab in combination with anlotinib in non-small cell lung cancer patients with uncommon EGFR mutations: A phase II, single-arm, prospective study.
ELCC 2022 21P.
Edited by: Youshi Reviewer: Youshi Typesetting: XY Execution: XY