ESMO 2021 Non-Small Cell Lung Cancer Research Highlights

The 2021 European Society of Medical Oncology Annual Meeting (ESMO 2021) will be held from September 16 to 21, local time
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As one of the most important conferences in the field of oncology, this year's ESMO annual meeting announced many new research data
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Here, Yimaitong counts the blockbuster research in the field of lung cancer for readers
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Session 1 Non-metastatic non-small cell lung cancer 1 IMpower010 study up to 60% of patients with stage I-III non-small cell lung cancer (NSCLC) will have disease recurrence
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IMpower010 is the first randomized phase III study.
The results announced at the 2021 ASCO annual meeting show that the addition of atilizumab to adjuvant chemotherapy after tumor resection for patients with stage II~IIIA NSCLC can significantly improve disease-free survival (DFS)
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This ESMO meeting announced the exploratory analysis of the study on the location of recurrence and treatment after recurrence
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The study enrolled 1280 NSCLC patients with stage IB-IIIA and ECOG PS 0-1 who had been completely resected
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The patient received up to four cycles (21 days/cycle) of cisplatin-based chemotherapy (plus pemetrexed, docetaxel, gemcitabine or vinorelbine)
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Subsequently, 1005 patients were randomly assigned to the atilizumab group at a ratio of 1:1 to 1200 mg Q3W (16 cycles or until disease recurrence or unacceptable toxicity) or the best supportive care (BSC) group
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The primary endpoint DFS was stratified in PD-L1 TC≥1% (SP263) stage II-IIIA patients, all subsequent randomized stage II-IIIA patients and ITT IB-IIIA stage patients
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The results of the study showed that in PD-L1 TC ≥ 1% in II-IIIA stage [HR (95% CI)=0.
66 (0.
50, 0.
88)] and all randomized II-IIIA stages [HR=0.
79 (0.
64, 0.
96) ] DFS in patients was statistically significant
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In all randomized stage II-IIIA patients, as the expression of PD-L1 increased, DFS improved: TC<1%, HR=0.
97 (0.
72, 1.
31); TC=1-49%, HR=0.
87 (0.
60, 1.
26); TC≥50%, HR=0.
43 (0.
27, 0.
68)
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Among stage II-IIIA patients with PD-L1 TC ≥ 1%, 73 patients (29%) in the atilizumab group relapsed, while 102 patients (45%) in the BSC group relapsed
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In this DFS interim analysis, the recurrence rate of the BSC group was higher than that of the atilizumab group, but there was no significant difference in the recurrence pattern between the two groups
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The CIT usage rate was higher in the BSC group after recurrence
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The 2COAST study is based on the PACIFIC study.
Duvalizumab (D) has been approved for the treatment of unresectable stage III NSCLC patients who have not progressed after receiving concurrent chemoradiotherapy (cCRT)
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COAST (NCT03822351) is a global phase II clinical study aimed at evaluating the efficacy and safety of duvalizumab alone or in combination with anti-CD73 monoclonal antibody oleclumab (O) or anti-NKG2A monoclonal antibody monalizumab (M) as a consolidation therapy Sex
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The study included patients with unresectable stage III NSCLC, ECOG PS 0-1 and no disease progression after concurrent radiotherapy and chemotherapy
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Within 42 days of cCRT treatment, patients randomly receive duvalizumab at a ratio of 1:1:1, combined with oleclumab 3000 mg IV Q2W (first 2 cycles, then Q4W) or monalizumab 750 mg IV Q2W, the longest Treatment for 12 months
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The primary study endpoint is the objective response rate (ORR), and the secondary endpoints are progression-free survival (PFS) and safety
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The results showed that the confirmed ORRs of the three cohorts D, D+O, and D+M were 17.
9%, 30.
0%, and 35.
5%, respectively; the median PFS of the three cohorts were 6.
3 months (3.
7-11.
2), NR (10.
4-NE), 15.
1 months (13.
6-NE); the 10-month PFS rates of the three cohorts were 39.
2%, 64.
8%, and 72.
7%, respectively
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The study showed that compared with D drugs alone, D+O and D+M can improve patients’ ORR, PFS and 10-month PFS rates
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The safety of patients in each group was similar, and no new safety incidents were found
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3GEMSTONE-301 study cCRT after immunotherapy is the standard treatment for patients with unresectable stage III NSCLC
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However, nearly half of patients cannot tolerate cCRT, so sequential CRT (sCRT) is widely used clinically
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The Phase III GEMSTONE-301 study data was announced at this ESMO meeting, aiming to evaluate the efficacy and safety of sugemalimab (PD-L1 monoclonal antibody) for stage III NSCLC patients whose tumors have not progressed after cCRT or sCRT treatment
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Eligible patients were randomized 2:1 and received sugemalimab 1200mg or placebo Q3W, according to ECOG performance score (0 vs 1), CRT type (cCRT vs sCRT) and total radiation dose (<60gy vs ≥60gy) Layer
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The primary endpoint was the PFS assessed by the Blind Independent Review Committee (BICR) according to RECIST v1.
1
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Among the 381 subjects randomly selected from 50 centers, 33.
3% received sCRT, 69.
6% of the subjects had an ECOG performance score of 1, and 69.
0% of the subjects had squamous cell carcinoma, 28% each / 55%/16% of subjects have stage IIIA/IIIB/IIIC disease
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In the pre-planned interim analysis, the median follow-up time was 14 months, the median PFS in the sugemalimab group was 9.
0 months, and the placebo group was 5.
8 months (HR 0.
64; 95%CI 0.
48-0.
85; P=0.
0026)
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The PFS rates of the two groups at 12 months and 18 months were 45% vs 26% and 39% vs 23%, respectively
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Whether the patients received sCRT (median PFS 8.
1 months vs 4.
1 months, HR 0.
59) or cCRT (median PFS 10.
5 months vs 6.
4 months, HR 0.
66), consistent PFS benefits were observed
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The overall survival (OS) data are not yet mature, but a trend of sugemalimab benefit has been observed (HR 0.
44; 95%CI 0.
27-0.
73)
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In the sugemalimumab group and the placebo group, the 12-month and 18-month OS rates were 89% vs 76% and 82% vs 60%, respectively, and 24.
3% of patients with emergency treatment adverse events (AE) ≥3 And 23.
8%
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The study showed that compared with placebo, the improvement in PFS of sugemalimab is statistically and clinically significant, and the safety is good
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These results provide evidence for the application of sugemalimab in patients with unresectable stage III NSCLC
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Session 2 Metastatic Non-Small Cell Lung Cancer 4WJOG9717L Study Osimertinib has become the standard treatment for newly treated EGFR-mutant NSCLC patients
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Previous studies have shown that adding anti-VEGF inhibitors to erlotinib can prolong PFS in patients with EGFR-mutant non-squamous NSCLC
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The phase II open-label randomized trial WJOG9717L study compared the efficacy of osimertinib combined with bevacizumab and osimertinib as a single agent in the treatment of patients with advanced EGFR-mutant non-squamous NSCLC
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This study included patients with advanced non-squamous NSCLC who were newly treated with EGFR sensitizing mutations (Del19 or L858R) and asymptomatic brain metastases
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Randomized according to a 1:1 ratio and received osimertinib (80 mg, daily) combined with bevacizumab (15 mg/kg, every 3 weeks) (OB group) or osimertinib monotherapy ( Group O), and stratified according to gender, stage and EGFR mutation status
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The primary endpoint was PFS as assessed by BICR
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From January 2018 to September 2018, a total of 122 patients were enrolled (61 in the OB group and 61 in the O group)
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At a median follow-up of 19.
8 months, the median PFS assessed by BICR in the OB group was 22.
1 months, the O group was 20.
2 months, and the HR was 0.
862 (60% CI, 0.
700-1.
060; 95% CI, 0.
531-1.
397; single Lateral stratification log-rank p=0.
213)
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In the subgroup analysis, the PFS trend of former smokers (HR 0.
481) and 19del patients (HR 0.
622) in the OB group was better
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The ORR of OB group was 82%, and that of O group was 86%
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Grade 3-4 AEs were observed in 34 patients in the OB group (56%) and 29 patients in the O group (48%)
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In the OB group, paronychia, acne-like rash, hypertension, epistaxis, and proteinuria of any grade often occurred
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Among them, 3% and 18% of OB group and O group had pneumonia of any grade, and 1 person in each group had grade 3 pneumonia
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 The study showed that for EGFR-mutant non-squamous NSCLC patients, osimertinib combined with bevacizumab failed to show improvement in initial PFS compared with osimertinib as a single agent
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  5DESTINY-Lung01 studies HER2 mutations in about 3% of NSCLC.
There is currently no approved HER2 targeted therapy for NSCLC patients, and this need remains to be realized
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The DESTINY-Lung01 (NCT03505710) study evaluated the efficacy and safety of T-DXd (antibody-drug conjugate) in patients with HER2-positive metastatic NSCLC
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 DESTINY-Lung01 is an ongoing multicenter phase II study aimed at exploring two cohorts of patients with unresectable/or advanced non-squamous NSCLC-HER2 overexpression (immunohistochemistry 2+ or 3+) and HER2 mutant NSCLC Efficacy of T-DXd posterior line therapy in the cohort
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Cohort 2 included patients with unresectable or metastatic non-squamous NSCLC who were relapsed or refractory to standard treatment.
Patients must have measurable lesions (according to RECIST v1.
1 criteria), asymptomatic central nervous system (CNS) metastases at baseline, ECOG performance status is 0 or 1 and locally reported HER2 mutations
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The primary endpoint of the study was ORR confirmed by an independent central review (ICR); secondary endpoints included duration of remission (DOR), PFS, OS, disease control rate (DCR), and safety
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The HER2 mutation is used as a predictive biomarker as an exploratory end point
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A total of 91 patients with HER2 mutant NSCLC were enrolled (data cut-off date is May 3, 2021)
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The median follow-up time was 13.
1 months, and the median age was 60 years
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93.
4% of subjects carried mutations in the HER2 kinase domain; 36.
3% of subjects had asymptomatic CNS metastases that did not require continuous treatment
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The median number of previous treatment lines for subjects who had previously participated in cancer treatment was 2 (range 0-7), including platinum therapy (94.
5%) and PD-1/PD-L1 therapy (65.
9%)
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The ORR confirmed by ICR was 54.
9% (95% CI, 44.
2-65.
4)
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The efficacy was consistent across all subgroups, including patients who had previously been treated with HER2 TKI or metastasized to the CNS
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The median PFS was 8.
2 months, and the median OS was 17.
8 months
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96.
7% of patients had treatment-related adverse events (TRAEs)
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Twenty-four patients (3 cases were grade 1, 15 cases were grade 2, 4 cases were grade 3, and 2 cases were grade 5) were judged to be drug-related interstitial lung disease (ILD)
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In addition, biomarker analysis also showed that disease relief caused by T-DXd was observed in patients with different HER2 mutation subtypes, and in patients with no detection of HER2 expression or HER2 gene amplification
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The study showed that T-DXd showed strong and long-lasting activity in previously treated HER2 mutant NSCLC patients, and its safety is consistent with previous studies
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Although more patients have experienced TEAEs, most TEAEs are well controlled through supportive treatment
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This study supports T-DXd as a new standard of potential treatment for patients with HER2 mutant NSCLC
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6ZENITH20-4 study EGFR and HER2 exon 20 mutant NSCLC treatment needs have not yet been met
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Poziotinib is a potent tyrosine kinase inhibitor (TKI) that can target EGFR or HER2 exon 20 insertion mutations
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ZENITH20 is a multi-cohort, multi-center, open-label trial designed to evaluate the efficacy, safety and tolerability of Poziotinib
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The ZENITH20 study included patients with advanced NSCLC with exon 20 insertion mutations: Cohorts 1, 2, 3, and 4 identified by the tumor tissue genetic profile were previously treated EGFR mutant patients and previously treated HER2 mutant patients.
, Newly-treated EGFR mutant patients and newly-treated HER2 mutant patients
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The treatment regimen is poziotinib (16 mg) orally once a day (QD) or twice a day (BID).
The dose can be interrupted/reduced due to toxicity
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The primary endpoint is the ORR assessed by the Independent Review Committee (ICR) according to RECIST 1.
1
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Secondary endpoints include DCR, DOR, PFS, and safety
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The data of cohort 4 was reported at this ESMO meeting
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Forty-eight subjects in cohort 4 received 16 mg poziotinib QD and 23 patients received 8 mg poziotinib BID
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The QD group data has been released, and the BID group is still registered
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Forty-eight subjects in the QD group have finished treatment, with a median age of 61 years (34-87 years), and 4 subjects are still undergoing research
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Most subjects were white (75%), women (54%), non-smokers (69%), and ECOG PS was 1 (65%)
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The dose was discontinued in 88% of patients, and the dose was reduced in 76% of the subjects compared to the initial treatment (16 mg)
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AE-related discontinuation occurred in 12% of patients
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The most common treatment-related grade 3 AEs were skin rash (35%), diarrhea (14%), stomatitis (20%), and pain (8%)
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With a median follow-up of 13.
5 months, the ORR was 43.
8% (95% CI: 29.
5%-58.
8%), of which 1 case (2.
1%) had a complete remission and 20 cases (41.
7%) had a partial remission
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Fifteen patients (31.
3%) were in stable condition, 7 patients (14.
6%) were in progress; 5 patients (10.
4%) were not evaluable
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The DCR is 75%
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The median DOR was 5.
4 months (range: 2.
8-19.
1+), and the 6-month and 1-year DoR rates were 42% and 24%, respectively
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The median PFS was 5.
6 months (range: 0-20.
2+), the 6-month PFS rate was 42%; the 1-year PFS rate was 26%
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The study showed that in newly diagnosed NSCLC patients with HER2 exon 20 mutations, the dose of poziotinib 16 mg QD showed a clinically significant therapeutic effect
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The security is similar to other second-generation TKIs, and its AEs are controllable
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The research on BID dose is still ongoing
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