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I will start by the overall survival analysis of the ADAURA study, which will be presented in the PLENARY SESSION. Since the announcement in March 2023 of an improvement in survival with adjuvant Osimertinib, it will be very interesting to see the actual survival improvements and whether this benefit is seen in all subgroups. As adjuvant therapy is predominantly about increasing cure rates and improving survival, these data will confirm that adjuvant Osimertinib is the standard of care. The question we might see at ASCO is in which subgroups does this survival benefit occur.
Overall survival analysis from the ADAURA trial of adjuvant osimertinib in patients with resected EGFR‑mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC).
Roy Herbst – Plenary Abstract LBA3
Now let's look at other abstracts, sorted by disease stage or subtype.
Early Lung Cancer:
There has been a significant change in the treatment of early stage NSCLC over the last couple of years with the introduction of neoadjuvant and adjuvant immunotherapy (IO). It is still unclear which patients should be treated with neoadjuvant chemo+IO or adjuvant chemo+IO (or perioperative chemo+IO). Will we hear some data from KEYNOTE 091, a study which has stirred much discussion surrounding the results, particularly in subgroups like high PDL-1 group and EGFR mutated patients. Maybe the data presented will shed some further light on this study.
We will also hear 3-year clinical outcomes from CHECKMATE 816. This has become a standard treatment for some resectable patients and I am looking forward to these updated results.
Samuel Rosner will present response data to neoadjuvant IO based therapy in oncogene driven resectable NSCLC. This data will be interesting as many of us are reluctant to prescribe IO in patients in the resectable setting even though there is no strong evidence to deny these patients this treatment. These data may validate our clinical hunch that IO is less effective the oncogene driven NSCLC, even in the early stage, or in turn, may question this assumption. At least this may give us some evidence to support or question our practice.
Pembrolizumab vs placebo for early stage non small cell lung cancer after resection and adjuvant therapy: Subgroup analysis of patients who received adjuvant chemotherapy in the phase 3 PEARLS/KEYNOTE-091 study. Kersti Oselin Poster discussion Abstract 8520
Clinical outcomes with neoadjuvant nivolumab (N) + chemotherapy (C) vs C by definitive surgery in patients (pts) with resectable NSCLC: 3-y results from the phase 3 Checkmate 816 trial. Jonathan Spicer Abtract 8521
Response to neoadjuvant immune checkpoint inhibitor (ICI)- based therapy in oncogene-driven resectable non-small cell lung cancer (NSCLC) Samuel Rosner Poster discussion Abstract 8523
Metastatic NSCLC
The transformation that has occurred over the last 10-15 years in the field of metastatic NSCLC has definitely changed the outcomes of many patients. The number of trials investigating NSCLC is remarkable and challenging to keep up. I have chosen a number of the abstracts that I think may have an impact on our patients and clinics earlier than later.
1st line wild-type NSCLC
Updated 4-year survival from the CHECKMATE 9LA trial will be presented including data by different histological subtypes. Will these data affect our choice of 1st line treatment in wild-type patients?
First line (1L) nivolumab (N) + ipilimumab (I) + chemotherapy (C) vs (C) alone in patients (pts) with metastatic NSCLC (mNSCLC) from Checkmate 9LA: 4-y clinical update and outcomes by tumor histologic subtyoe (THS) David Paul Carbone Poster discussion LBA9023
Previously treated non-molecularly driven NSCLC
This is a tough area with few efficacious treatments available and we are awaiting some breakthroughs in this cohort of patients. There are 2 studies which I picked for this cohort of patients with a relatively poor prognosis. Datopotamab deruxtecan, a TROP2 directed antibody drug conjugate, which has shown some positive early results in breast cancer and previous results of this compound in NSCLC has shown responses in combination with pembrolizumab (with or without chemotherapy) in previously untreated and treated NSCLC. Am waiting to see if data for previously untreated and treated patients will be presented and will this provide us with other options in our patients.
Another interesting study is the phase 3 LUNAR study investigating the addition of Tumor Treating Fields (TTF) to standard of care in previously treated NSCLC. TTF is approved for treatment of Glioblastoma and pleural mesothelioma. Can this device improve outcomes in this difficult to treat resistant/refractory patients? Will it be practical? Will subgroup analysis identify which patients may benefit?
TROPION-Lung02: Datopotamab deruxtecan (Dato-Dxd) plus pembrolizumab (pembro)with or without platinum chemotherapy (Pt-CT) in advanced non small cell lung cancer (aNSCLC) Yasushi Goto Oral Abstract 9004
Tumor treating fields (TTFields) therapy with standard of care (SOC) in metastatic non small cell lung cancer (mNSCLC) following platinum failure: Randomized, phase 3 LUNAR study LBA 9005
Moleculary driven NSCLC
KRAS
Sotorasib definitely has some efficacy in previously treated metastatic KRAS G12C NSCLC. Unfortunately the CodeBreaK 200 study did not show an overall survival benefit. Will we be able to see subgroups that may benefit more from sotorasib than docetaxel. Presentations of the intracranial efficacy versus docetaxel will be presented and a biomarker analysis will also be presented. Can these data select certain patients that may preferentially benefit from sotorasib?
Intracranial efficacy of sotorasib versus docetaxel in pretreated KRAS G12C mutated advanced non small cell lung cancer (NSCLC): Practice informing data from a global, phase 3, randomized, controlled trial (RCT). Anne-Marie C. Dingemans LBA9016
Biomarker subgroup analysis if CodeBreak 200, a phase 3 trial of sotorasib versus (vs) docetaxel in patients (pts) with pretreated KRAS G12C mutation advanced non small cell lung cancer (NSCLC) Ferdinandos Skoulidis Abstract 9008
EGFR
Treating patients with metastatic EGFR mutated NSCLC with progression after Osimertinib is also a difficult decision for clinicians and patients. There are no clear data to prefer one treatment over another and many clinicians try to recruit patients to clinical trials after progression. Others recommend further genomic profiling to attempt to identify resistance mechanisms and potentially treat according to the resistance mechanism identified. Two very interesting studies will be presented in TKI progressing cohort of patients. Does the addition of pembrolizumab to platinum based chemotherapy have a role in this cohort with EGFR driven tumors? The KEYNOTE-789 will provide this important and relevant clinical question.
It is well documented that MET amplification is a common resistance mechanism to the EGFR TKI Osimertinib. Previous data on the combination of tepotinib and Osimertinib has been presented but additional data will further our understanding on this combination's role in Osimertinib refractory EGFRmut NSCLC.
Pemetrexed and platinum with or without pembrolizumab for tyrosine kinase inhibitor (TKI) resistant, EGFR mutant metastatic nonsquamous NSCLC: Phase 3 KEYNOTE-789 study James Chih-Hson Yang Oral abstract LBA9000
Tepotinib + Osimertinib for EGFR mutant (EGFRm) NSCLC with MET amplification (METamp) after first line Osimertinib. Daniel Shao-Weng Tan Poster discussion 9021
Other molecularly driven NSCLC
Two other studies caught my attention. The efficacy of repotrectinib in advanced ROS1 fusion positive NSCLC. We already have 2 approved agents for ROS1+ NSCLC and data has been presented regarding the efficacy of repotrectinib, both in TKI naïve and TKI previously treated cohorts. This updated data from the TRIDENT trial will provide more data in this relatively rare subset.
And we also have a new combination of BRAF/MEK inhibitors in the NSCLC arena. Will the efficacy of encorafenib/binimetinib (PHAROS study) be similar to the dabrafenib/trametinib data, as seen in melanoma, or will there be a difference (taking into account cross trial differences). If the results are similar, it may provide another option with a different safety profile.
Intracranial and systemic efficacy of repotrectinib in advanced ROS1 fusion positive (ROS1+) non small cell lung cancer (NSCLC) and central nervous system metastases (CNS mets) in the phase 1/2 TRIDENT-1 Jessiva Jiyeong Poster discussion Abstract 9017
Efficacy and safety of encorafenib (enco) plus binimetinib (bini) in patients with BRAF V600E mutant (BRAFV600E)metastatic non small cell lung cancer (NSCLC) from the phase 2 PHAROS study. Gregory Riely Poster discussion 9018
Mesothelioma
We are awaiting the results of the IND227 study since the press release in March announced that the addition of pembrolizumab to chemotherapy in malignant pleural mesothelioma improves survival. May there finally be a new standard of care for epithelioid mesothelioma? It will be interesting to see subgroup analyses and how will this effect our treatment recommendations, including those with sarcomatoid mesothelioma?
IND227 phase III (P3) study of cisplatin/pemetrexed (CP) with or without pembrolizumab (pembro) in patients (pts) with malignant pleural mesothelioma (PM): A CCTG, NCIN and IFCT trial. Quincy Chu Oral abstract session LBA8505
Small cell lung cancer
Limited small cell –
There is still much debate as to what radiation dose and fractionation is practical and should be given to patients with limited stage SCLC. Not sure if this trial will change our practice but will be interesting to see whether higher doses of RT translated into improved outcomes or will it be like the RTOG 0617 trial in NSCLC?
Final survival data from a randomized phase II trial comparing high dose with standard -dose twice daily (BID) thoracic radiotherapy (TRT) in limited stage small cell lung cancer (LS SCLC) Bjorn H. Henning Gronber Poster discussion Abstract 8512
Extensive SCLC - is there a role for targeted therapy?
Over many years, few trials have been positive in the extensive small cell arena. The addition of IO to 1st line chemotherapy has been associated with improved outcomes but unfortunately there are no biomarkers that can help select which patients achieve a significant benefit from the addition of IO. Will an exploratory analysis of KEYNOTE 604 provide some data?
Other studies are also looking at biomarker selected SCLC or targeted therapies in SCLC. Hoping these will bring some hope to this patient group with a poor prognosis. Despite previous disappointing data with Rovalpituzumab teserine in the DLL3+ SCLC patients as a monotherapy, some data looking at the combination of Rova-T with immunotherapy looked promising. Will BI 764523 show us some promising results? Will SLFN11 become a predictive biomarker for PARP inhibition (with IO) in SCLC? Are PARP inhibitors and IO effective for unselected SCLC patients? Will there be a role for antibody-drug-conjugates in SCLC? Some of these abstracts may provide some answers to these questions.
Exploratory biomarker analysis of the phase 3 Keynote-604 study of pembrolizumab plus etoposide for extensive stage SCLC Charles Rudin Oral Abstract Session 8503
First in human dose escalation trial of BI 764523, a delta-like ligand 3 (DLL3)/CD3 IgG-like T cell engager in patients (pts) with DLL3-positive (DLL3+) small cell lung cancer (SCLC) and neuroendocrine carcinoma (NEC). Martin Wermke Oral abstract session Abstract 8502
SWOG S1929: Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer (ES-SCLC) Nagla Fawzy Abdel Karim Oral Abstract Session 8504
Phase II study of durvalumab plus Olaparib as maintenance therapy in extensive-stage small cell lung cancer (TRIDENT): Preliminary efficacy and safety results . Yan Huang Poster Discussion Abstract 8518 (Poster bd 145)
First in human study of ABBV-011, a seizure related homolog protein 6 (SEZ6)-targeting antobody-drug conjugate, in patients with small cell lung cancer Daniel Morgensztern Oral Abstract 3002
General topic
We all feel the pain when discussing the topic of time to molecular testing results and waiting to start the most effective treatment for metastatic NSCLC. Can the implementation of early liquid biopsies improve outcomes? Does timely targeted therapy have a clinical value? Follow these 2 abstracts to learn some more.
LIBELULE: A randomized phase III study to evaluate the clinical relevance of early liquid biopsy (LB) in patients with suspicious metastatic lung cancer. Aurelie Swalduz Poster discussion 9019
Clinical value of timely targeted therapy (TT) for patients with advanced non small cell lung cancer (aNSCLC) with actionable driver oncogenes) Thomas Stricker Abstract 6507
In summary, oncology has become such a diverse and complicated specialty in medicine with progress occurring at a pace that is difficult to keep up with. General oncology conferences cover so many topics that it is easy to get lost. I hope this list will help those interested in Thoracic Oncology to find some interesting and useful abstracts.
Looking forward to hearing these data and hopefully implementing some of them into my practice to improve patient outcomes.
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