ELCC 2022
Lecture Board: Maximilian Hochmair, MD; Jordi Remon, MD, PhD; Fred R. Hirsch, MD, PhD
Publishing Editor: Anna Fenzl, PhD
Preface
The European Lung Cancer Congress (ELCC) that took place virtually on 30th March – 2nd April 2022 effectively disseminated the latest advances in lung and thoracic malignancies and gave 131 speakers from all around the world the chance to present promising new research avenues as well as the opportunity for discussions and new perspectives.
Looking more closely at upcoming and established immunotherapy standards
Adjuvant treatment using immune checkpoint inhibition after complete resection of early-stage lung cancer is being investigated considering the modest survival benefit conferred by platinum-based combination chemotherapy in this setting. IMpower010 was the first phase III immunotherapy study to demonstrate a significant disease-free survival (DFS) improvement in the adjuvant setting after platinum-based chemotherapy. Patients included in this trial had undergone complete resection of stage IB-IIIA NSCLC and subsequently received 1–4 cycles of cisplatin-based chemotherapy.
Oncogene-driven lung cancer: EGFR, METex14, ROS1, RET
The neoadjuvant potential of the third-generation EGFR TKI osimertinib was assessed in the multicenter, single-arm, phase II NEOS study that included patients with resectable, stage II-IIIB N2, EGFR-mutant (ex19del/L858R) adenocarcinoma of the lung. Forty patients received osimertinib 80 mg QD for 6 weeks prior to surgery.
SCLC: prognostic determinants and new treatment modalities
The global, randomized, open-label, phase III CASPIAN trial was initiated to test the anti-PD-L1 antibody durvalumab with or without the CTLA-4 inhibitor tremelimumab in addition to etoposide-platinum chemotherapy (EP) as first-line treatment in patients with extensive-stage small-cell lung cancer (ES-SCLC).
EXPERT VIDEOS
All video interviews from ELCC 2022
Jordi Remon outlines what needs to be considered in the context of neoadjuvant and adjuvant immunotherapy in patients with resectable lung cancer, how tyrosine kinase inhibitors can contribute to effective perioperative treatment, treatment approaches in patients with oncogene-driven lung cancer who develop brain metastases as well as in patients with CNS affection whose tumors do not harbor genetic drivers. Current challenges in selecting the best immunotherapeutic approach for the individual patient with mNSCLC and how to deal with them as well as promising potential predictive biomarkers of ICI in patients with NSCLC are highlighted, too.
Lizza Hendriks discusses how clinical trials should be adapted considering the increasing use of brain metastasis screening in lung cancer patients, the immune micro-environment of CNS metastases, the role of the treatment sequence in the management of patients with brain lesions and summarizes how patients with low PD-L1 expression, frail/elderly patients and those with actionable mutations can be addressed, followed by depicting novel biomarkers for precision immunotherapy.
Jarushka Naidoo depicts recent developments in the first-line therapy of limited-stage small cell lung cancer (SCLC), treatment options for patients with newly diagnosed extensive-stage SCLC, agents emerging for the management of patients with platinum-refractory disease, the molecular types of SCLC and how they respond to targeted therapies and ICIs and gives an overview of the greatest difficulties in the field of irAEs.
At this year’s conference, which took place in Geneva from 10th to 13th April, more than 120 speakers shared their knowledge with around 1,600 delegates from 75 countries. The comprehensive program that included a wide range of session types and the presentation of 210 abstracts aimed at conveying a broad view of the current knowledge ranging from screening and the very early disease to current and potential future treatment approaches for different types of thoracic tumors.
ELCC 2019 – Geneva
Lecture Board: Anne-Marie Dingemans, MD, PhD; Pilar Garrido, MD, PhD; Maximilian Hochmair, MD; Nir Peled, MD, PhD
Medical Writer: Dr. Judith Moser
Preface – ELCC 2019
Preface – ELCC 2019 Pilar Garrido, MD, PhD Head of the Thoracic Tumor Section, Medical Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain …
...Current perspectives in EGFR-targeted therapy
Current perspectives in EGFR-targeted therapy Global phase IIIb study assessing afatinib The second-generation, irreversible ErbB family blocker afatinib has been established as a first-line standard option in patients with EGFR-mutant NSCLC based on the phase III LUX-Lung 3 and 6 trials that revealed significant progression-free survival (PFS) and objective response rate (ORR) improvement compared to platinum-doublet chemotherapy [1, 2]. …
...Immunotherapy: analyses elucidating durvalumab & pembrolizumab activity
Immunotherapy: analyses elucidating durvalumab & pembrolizumab activity PACIFIC: OS after subsequent immunotherapies The phase III, randomized, double-blind, international PACIFIC trial established durvalumab in the treatment of patients with stage III, unresectable NSCLC without progression after definitive platinum-based concurrent chemoradiotherapy. …
...Encouraging findings in NTRK-, ROS1– and ALK-positive lung cancer
Encouraging findings in NTRK-, ROS1– and ALK-positive lung cancer TRK inhibition: larotrectinib Neutrotrophic receptor tyrosine kinase (NTRK) gene fusions occur in a wide array of different cancers including rare entities such as infantile fibrosarcoma, but also in common tumors including melanoma, colon cancer, and lung cancer [1]. …
...Interview: Improving accuracy of lung cancer screening
Interview: Improving accuracy of lung cancer screening Nir Peled, MD PhD, The Legacy Heritage Oncology Center & Dr. Larry Norton Institute, Soroka Medical Center & Ben-Gurion University, Beer-Sheva, Israel …
...Extensive-disease small-cell tumors: signals of activity
Most of the patients with small-cell lung cancer (SCLC) are diagnosed in the extensive-disease stage (ED-SCLC). They generally respond well to first-line platinum-based chemotherapy; however, responses are not durable, and prognosis is poor. In the second line and beyond, the NCCN guidelines recommend patient inclusion in a clinical trial, systemic therapy depending on the patient performance status and the duration of the relapse-free interval, or palliative symptom management.
Interview: “We need chemotherapy when rapid responses are required”
As the relative importance of chemotherapy in NSCLC management is changing, how can chemotherapeutic agents contribute to increasing efficacy in the context of new treatments?
Anti-angiogenic combinations excel in later lines
The ongoing, prospective, non-interventional VARGADO study is assessing the angiokinase inhibitor nintedanib plus docetaxel in patients with advanced adenocarcinoma of the lung after first-line chemotherapy in routine clinical practice. VARGADO is conducted at approximately 100 sites across Germany and includes 3 cohorts.
Interview: “We need chemotherapy when rapid responses are required”
As the relative importance of chemotherapy in NSCLC management is changing, how can chemotherapeutic agents contribute to increasing efficacy in the context of new treatments?
序言
一年一度的欧洲肺癌大会已成为全球性会议,吸引了世界各地肺癌领域专家的参与。本年度会议于4月10日至13日在日内瓦召开,超过120位发言人在会上与来自75个国家的约1,600名代表分享了他们的知识经验。此次综合性大会包括各种类型的会议并推介了210篇摘要,旨在传达范围广泛的现有知识,从筛查和非常早期的疾病到针对不同类型胸部肿瘤的当前和未来潜在治疗方法。
对于EGFR靶向治疗的当前观点
基于III期LUX-Lung 3和6试验,第二代不可逆ErbB家族阻断剂阿法替尼已被确定为EGFR突变NSCLC患者的一线标准选择,该试验显示出与铂双药化疗相比显著的无进展生存期(PFS)和客观缓解率(ORR)改善。此外,IIb期LUX-Lung 7研究显示,与第一代EGFR酪氨酸激酶抑制剂(TKI)吉非替尼(gefitinib)相比,阿法替尼在PFS、ORR和至治疗失败时间方面有显著获益。
免疫疗法:分析阐明度伐鲁单抗和派姆单抗活性
III期随机化双盲国际PACIFIC试验在根治性铂类同步放化疗后未经历进展的III期无法切除NSCLC患者中确立了度伐鲁单抗治疗。在放化疗后6周内, 将患者随机分配为每2周(Q2W) 10 mg/kg 度伐鲁单抗达最多12个月 (n = 476)或匹配安慰剂(n = 237)。
NTRK-、ROS1-和ALK-阳性肺癌中令人鼓舞的发现
NTRK-、ROS1-和ALK-阳性肺癌中令人鼓舞的发现 TRK抑制:拉罗替尼(larotrectinib) 神经营养受体酪氨酸激酶(NTRK)基因融合发生在包括诸如婴儿纤维肉瘤等罕见肿瘤的多种不同的癌症中,但也存在于包括黑素瘤、结肠癌和肺癌在内的常见肿瘤中 [1]。它们在肺癌中的发病率估计为0.2 %至3.3 %[1,2]。高选择性的口服CNS活性TRK抑制剂拉罗替尼已被美国食品药品监督管理局批准用于治疗患有显示NTRK融合的实体瘤的成人和儿童患者。Drilon等人介绍了来自11名TRK融合阳性肺癌患者的汇总数据,这些患者在针对晚期实体肿瘤进行的I期研究和II期篮子试验中接受了拉罗替尼[3]。5名患者先前接受过1种或2种全身治疗,5名患者曾经接受过3种或更多种治疗。治疗包括连续100 mg每日两次拉罗替尼。 事实上,该分析证明了拉罗替尼在携带TRK融合的晚期肺癌中的活性。7名患者(71 %)发生缓解,其中分别有1名和4名患者经历完全缓解(CR)和部分缓解(PR)。在2例病例中发生了疾病稳定。没有患者发生原发性疾病进展。在分析时尚未达到缓解的中位持续时间。此外,拉罗替尼显示颅内 ...
提高肺癌筛查的准确性
毫无疑问,戒烟是初级预防的目标,但是一旦发现患者吸烟或曾经吸烟,应尽可能进行早期检测。目前经验证的用于此目的的平台之一是低剂量计算机断层扫描。然而,我们的目标是在该平台之外添加分子生物标志物以提高特异性甚至灵敏度。存在来自不同身体隔室的一系列大有前景的生物标志物。
广泛期小细胞肿瘤:活性信号
大多数小细胞肺癌(SCLC)患者在广泛期(ED-SCLC)得以诊断。它们通常对一线铂类化疗反应良好;然而,反应并不持久,且预后较差。在二线及以后,NCCN指南建议患者参与临床试验,取决于患者的表现状态和无复发间隔持续时间的全身治疗,或姑息症状管理。 目前没有可用的维持治疗来延长一线化疗获得的效果。CheckMate 451试验设计用于评估这种条件下的免疫疗法。
“当需要快速缓解时,化疗必不可少”
在过去几年中,由于引入了诸如靶向药物等新药物和免疫疗法,肺癌患者的治疗得到了极大改善。然而,所有数据都显示这些治疗并不适用于所有患者。因此,我们仍然需要化疗。例如,在多线治疗后发生多重耐药时,化疗对于诱导具有驱动突变患者的全身反应可能必不可少。
抗血管生成组合在后线中表现优异
正在进行的前瞻性非干预性VARGADO研究在常规临床实践中评估血管激酶抑制剂尼达尼布加多西他赛在一线化疗后晚期肺腺癌患者中的作用。VARGADO在德国的约100个地点进行,包括3个队列。队列A分别在一线和二线条件下接受化疗和尼达尼布加多西他赛;对于队列B,免疫检查点抑制(ICI)构成化疗后的二线治疗,然后接受尼达尼布组合;在队列C中,在一线给予化疗加ICI治疗,并且在二线给予尼达尼布加多西他赛(图1)。
巻頭言
臨床医の皆様へ 欧州肺癌学会議は、肺がんに治療に携わる、世界各国の専門医の注目を集める世界会議となっています。4月10日から13日までジュネーブで行われた本年度の会議には、75か国から参加したおよそ1600名の専門家を前に120名を超える発表者がこれまでに得た知見を発表しました。
EGFR阻害薬への現在の評価
第二世代の不可逆的ErbBファミリー阻害薬であるアファチニブが、EGFR遺伝子変異陽性NSCLC患者へのファーストライン治療の標準薬になりうることが証明された。その根拠となったのは、LUX-Lung3および6の第Ⅲ相試験で見られた、プラチナダブレット療法に対する無増悪生存期間(PFS)と無増悪生存率(ORR)の顕著な改善である。
免疫療法:デュルバルマブおよびペムブロリズマブの作用が分析により明らかに
切除不能なⅢ期のNSCLC患者で、プラチナ製剤ベースの根治的放射線化学療法を受けた後に無増悪の状態が持続している患者にはデュルバルマブ療法を行うことが、国際共同第Ⅲ相ランダム化二重盲検プラセボ対照試験であるPACIFIC試験で確立した。放射線化学療法の実施から6週間以内に、患者をデュルバルマブ10 mg/kgを隔週(Q2W)で最長12か月間投与する群(n=476)もしくは、プラセボを投与する群(n=237)にランダムに割り付けた。
NTRK、ROS1、ALKの融合遺伝子陽性肺がんへの良好な成績が 判明
神経栄養因子チロシンキナーゼ受容体(NTRK)融合遺伝子は、乳児型線維肉腫のようなまれながんだけではなく、悪性黒色腫や大腸がん、肺がんといった一般的ながんも含め、多種多様ながんに発現している。肺がんでの発現率は0.2~3.3%と推測されている。
肺がん検診の精度を高める
一次予防ということではまず禁煙が目標ですが、患者さんが喫煙者や元喫煙者ということであれば、できる限り早期発見に努める必要があります。肺がんの早期発見に役立つということが現在分かっているのは低線量CTですが、この検査の特異度はもとより感度も改善させるために、分子バイオマーカーを加えることを目標にしています。
進展型小細胞肺がん:免疫療法の効果のシグナル
小細胞肺がん(SCLC)患者の大部分は進展型の段階で(ED-SCLC)診断を受けている。通常はファーストライン治療のプラチナ製剤ベースの化学療法に良く反応するが、その効果はしっかりとしておらず、予後も良好とはいえない。NCCNガイドラインはセカンドライン以降の治療に、治験への参加、パフォーマンスステータスと無再発生存期間にもよるが全身療法、緩和療法を推奨している。
「迅速な効果を求める場合には化学療法が必要」
肺がん患者さんへの治療法は分子標的治療薬や免疫療法といった新薬の登場で、ここ数年の間に大きく改善しています。しかし、いずれのデータを見てもすべての患者さんに効果を現しているわけではないので、化学療法がまだ必要になるのです。
セカンドライン治療以降の血管新生阻害薬の併用療法に良好な 結果
実施中の非介入前向き研究であるVARGADO試験では、実臨床で進行肺がんにファーストライン治療の化学療法を受けた患者を対象に、血管新生阻害薬のニンテダニブとドセタキセルの併用療法を評価している。同試験はドイツ国内の約100施設で、3つの患者コホートを対象に行われている。コホートAにはファーストライン治療に化学療法を、セカンドライン治療にはニンテダニブ+ドセタキセルの併用療法を行った。
EXPERT VIDEOS
All video interviews from ELCC 2019
Pilar Garrido gives an overview of the management of patients with stage III NSCLC, novel treatments in stage III disease and recent insights concerning immune modulatory vaccination in patients with NSCLC.
Thomas Newsom-Davis on the treatment algorithm for ALK-positive NSCLC and future developments for patients with ALK/ROS1-positive tumors.
Nir Peled talks about the importance of early detection of lung cancer – especially in poorer countries –, promising biomarkers for the early detection and new insights into the interactions between lung cancer cells and the tumor microenvironment.
Nir Peled talks about the importance of early detection of lung cancer – especially in poorer countries –, promising biomarkers for the early detection and new insights into the interactions between lung cancer cells and the tumor microenvironment.
At this year’s conference, which took place in Geneva from 10th to 13th April, more than 120 speakers shared their knowledge with around 1,600 delegates from 75 countries. The comprehensive program that included a wide range of session types and the presentation of 210 abstracts aimed at conveying a broad view of the current knowledge ranging from screening and the very early disease to current and potential future treatment approaches for different types of thoracic tumors.