ELCC2021: These advances in lung cancer treatment, you need to know

*Only for medical professionals to read for reference, come and learn together! The European Lung Cancer Conference (ELCC) is jointly organized by the most important multidisciplinary societies representing thoracic oncologists [European Medical Oncology (ESMO), International Association for Lung Cancer Research (IASLC), etc.
] to promote scientific development, disseminate education, and improve the overall The practice level of lung cancer experts in the world.

The 2021 European Lung Cancer Conference (ELCC 2021) will be held in the form of an online conference from March 25th to 27th.

A few days ago, the summary content has been published on the ELCC official website.

What are the exciting contents of this conference? Follow the editor to take a look! 01 China's lung cancer immunotherapy may add a new "Rayleigh" weapon (96O) The domestic PD-1 inhibitor carrelizumab currently has multiple indications in China.
This study aims to evaluate the first-line carrelizumab The efficacy and safety of combined chemotherapy in patients with squamous cell carcinoma.

The speaker is Professor Zhou Caicun from the Department of Oncology, Shanghai Pulmonary Hospital.

 This is a randomized, double-blind, placebo-controlled, multi-center Phase III clinical study, including newly treated patients with stage IIIb or IV squamous non-small cell lung cancer (NSCLC).

According to the ratio of 1:1, they were randomly divided into a combined carrelizumab group or a chemotherapy group.

Patients in the chemotherapy-only group were allowed to undergo crossover after progression.

The primary endpoint is the progression-free survival (PFS) assessed by the investigator.

A total of 389 patients were enrolled in this study, and the PFS of the two groups were 8.
5 months and 4.
9 months (HR 0.
37, P<0.
001).

Regardless of the PD-L1 expression level, patients can benefit.
Patients with PD-L1 expression less than 1% and greater than 1% have HRs of 0.
49 and 0.
34, respectively. The median overall survival (OS) of the two groups was unreached and 14.
5 months (HR 0.
55, P＜0.
001).

From the perspective of safety, the incidence of treatment-related adverse events of grade 3 and above in the two groups was 73.
6% and 71.
9%, respectively.

 Overall, for patients with locally advanced or metastatic squamous NSCLC with negative driver genes, carrelizumab combined with chemotherapy can improve the PFS and OS of the patients, and the safety is tolerable.
This scheme may become such a solution.
The new first-line standard treatment plan for patients.

02KEYNOTE-407 struck again and the 3-year follow-up data was announced (97O) This meeting released the 3-year follow-up data of the KEYNOTE-407 study.

The KEYNOTE-407 study is a multicenter, randomized, double-blind, placebo-controlled phase III clinical study, which aims to evaluate pembrolizumab or placebo combined with carboplatin and paclitaxel/albumin paclitaxel for stage IV squamous Efficacy and safety of first-line treatment for NSCLC patients.

 In the KEYNOTE-407 study, patients were randomly divided into pembrolizumab combined chemotherapy or placebo combined chemotherapy groups at a ratio of 1:1, with 1% PD-L1 expression as a stratification factor, and the main study endpoint was OS And PFS.

  The study showed that the median OS of the two groups were 17.
2 months and 11.
6 months (HR 0.
71), and the 3-year OS rates were 29.
7% and 18.
2%; the median PFS2 of the two groups were 13.
8 months and 9.
1 months, respectively (HR 0.
59); the median PFS was 8.
0 months and 5.
1 months (HR 0.
59), and the 3-year PFS rates were 16.
1% and 6.
5%, respectively.

In terms of safety, the incidence of treatment-related adverse reactions of grade 3 and above in the two groups was 74.
8% and 70.
0%, respectively.

 The results of the 3-year follow-up showed that pembrolizumab combined with chemotherapy can bring sustained benefits to patients compared with chemotherapy alone.

03What is the benefit of patients with different TMB expressions? (80O) Tumor mutational burden (TMB) can predict the efficacy of immune checkpoint inhibitors.
Therefore, the researchers evaluated the correlation between TMB levels and patient efficacy in the CheckMate-9LA study. The researchers measured TMB levels in tissues and peripheral blood.
A total of 711 randomized patients had TMB data.

Between the tTMB≥10 and <10 mut/Mb subgroups, and between the bTMB≥16 and <16 mut/Mb subgroups, double immunity + 2 weeks chemotherapy compared with 4-week chemotherapy showed similar benefits for OS .

Compared with bTMB<20µmut/Mb, the bTMB≥20 subgroup observed a higher OS benefit.

In addition, compared with patients with high TMB expression, patients with PFS and objective response rate (ORR) benefit more significantly.

04MRTX-849 impacts KRASG12C mutation in advanced NSCLC (99O) MRTX-849 is a drug that can irreversibly covalently bind to the KRAS G12C mutation site.
This meeting announced the efficacy and safety study of MRTX-849, and analyzed and evaluated it.
Correlation between co-mutation and patient efficacy.

 The study is a multi-cohort phase I/II clinical study, which aims to evaluate the efficacy and safety of the drug in patients with advanced or metastatic solid tumors.

A total of 79 patients with treated NSCLC received the recommended dose (600 mg).

Common treatment-related adverse events included nausea (54%), diarrhea (48%), vomiting (34%), fatigue (28%), and elevated alanine aminotransferase (ALT) (23%).

Fifty-one patients can be evaluated for efficacy, and 23 patients are evaluated as partial remission (PR), with an ORR of 45%.

 In conclusion, for patients with advanced NSCLC who have been treated for the KRAS G12C mutation, MRTX-849 shows acceptable safety and has certain activity.

05Platinum-sensitive NSCLC, olaparib maintenance therapy (100MO) The PIPSeN study evaluated the efficacy of olaparib maintenance therapy in patients with platinum-sensitive advanced NSCLC.

A total of 182 patients were included in the study, of which 60 patients were randomly assigned to the olaparib group (group O, n=33 cases) and the placebo group (group P, n=28 cases).

The study is divided into an induction phase and a maintenance treatment phase.
In the induction phase, 4 to 6 courses of platinum-containing dual-drug chemotherapy are given to all patients, and patients with partial or complete remission are randomly assigned to receive olaparib or placebo maintenance treatment until There is disease progression or unacceptable toxicity.

  The study showed that the median PFS of group O and group P were 2.
3 months and 2.
1 months, respectively (HR 0.
89, p=0.
68).

The median OS of group O and group P were 9.
5 months and 14.
1 months, respectively (HR 1.
29, p=0.
44).

In terms of safety, the incidence of ≥ grade 3 adverse events was 42.
4% in group O and 14.
8% in group P.

 Although well tolerated, maintenance therapy with olaparib did not improve the median PFS or median OS in patients with platinum-sensitive NSCLC.

06PACIFIC-R: What about the real-world patient characteristics of Duvalizumab in the treatment of stage III NSCLC revealed (79MO) in patients who use the PACIFIC regimen in the real world? The PACIFIC-R (NCT03798535) study published on ELCC explored this.

This is a large international observational study involving patients with unresectable stage III NSCLC who have received at least one dose of Vallizumab (10μmg/kg Q2W).

The patient has completed concurrent platinum-containing chemotherapy (cCRT) or sequential (sCRT) radiotherapy within the past 12 weeks, and there is no evidence of disease progression.

Data will be collected retrospectively to 5 years after selection.

 In the full analysis set (n=1155), the baseline demographics and disease characteristics of patients with different PD-L1 expression states (≥1%, n=574; <1%, n=138) were not significantly different.

Most patients received cCRT (n=893).

Patients receiving sCRT (n=163) are usually older (age ≥70 years: 37.
4% vs 28.
4%), and the proportion of tumors with larger tumors is higher (> 70mm: 25.
0% vs 15.
9%). The median total radiotherapy dose (overall: 65 Gy) and duration (overall: 1.
5 months) reflect local clinical practice.

In terms of platinum-containing chemotherapy regimens, vinorelbine is favored in France, Germany, and the United Kingdom; Australia and Israel prefer paclitaxel; and the Netherlands, Belgium, and Norway are etoposide.

The median duration of chemotherapy was 0.
8 to 2.
3 months (overall: 1.
6 months).

The median time from the end of CRT to the start of duvalizumab ranged from 39 to 89 days (overall: 52 days).

During the first 3 months of duvalizumab treatment, most of the reported adverse events of special concern (AESIs) were pneumonia (10.
6%) and endocrine lesions (6.
8%), which caused permanent damage in 4.
8% and 0.
2% of patients, respectively.
Discontinue the drug.

The results of this study show that the real-world characteristics of patients in the PACIFIC-R study are generally consistent with those of the PACIFIC study (only cCRT is allowed).

07ASTEROID: For patients with early stage NSCLC, SBRT sequential valizumab is safe and feasible (63MO) Stereotactic body radiotherapy (SBRT) is the standard treatment for early stage NSCLC patients who are not suitable for surgery.
It has excellent efficacy in local control.

But about 30% of patients will eventually develop distant metastases.

ASTEROID is a randomized, multicenter, open-label Phase II study to evaluate whether duvalizumab can improve the outcome of T1-2N0M0 NSCLC patients after SBRT.

At this year's ELCC, the study published the toxicity report of the first 47 patients for the first time.

 In this study, patients were randomized to receive SBRT alone (3 to 4 divided) treatment (group A) or SBRT sequential valizumab (1500 mg, once every 4 weeks) (group B).

The primary endpoint is time to progression (TTP).

So far, 25 and 22 patients have been enrolled in group A and group B, respectively.

Among them, 66% were women and 66% were adenocarcinoma; 28% had PS 0 points, 51% had PS 1 points, and 21% had PS 2 points.

The median age was 76 (58-89) years, 98% of patients had smoked before or now, and the average FEV1 was 1.
6 (0.
64~4.
5) L.

Among the 24 patients who completed the treatment, the median number of infusions of duvalizumab was 11 (3-12) times; in all patients studied, it was 6 (1-12) times.

In terms of safety, 7 (28%) and 6 (27%) patients in group A and group B respectively reported adverse events related to SBRT (CTCAE v4.
0).

These adverse events were grade 1 to 2, including pneumonia, cough, dyspnea, skin reactions, fatigue, and pain.

In group B, 12 patients (55%) reported adverse events related to duvalizumab, mainly grade 1 and 2, of which the most common were skin reaction/rash (45%), pruritus (27 %) and thyroid disease (18%).

Two patients experienced grade 3 pneumonia, 1 case of grade 3 dyspnea, 3 cases of grade 3 asymptomatic hepatitis, and 1 case of grade 4 asymptomatic lipase increase.

The results of this study indicate that SBRT sequential valliumab is feasible and well tolerated.

The study is still recruiting patients to assess the primary endpoint of TTP.

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