By Rashmi Acharya, MS; Andrew Ciupek, PhD; Jennifer C. King, PhD; and Daniel Saez, MSc 

The annual meeting held by the American Society of Clinical Oncology (ASCO) is the stage for presenting many of the most impactful advancements in cancer research – including in lung cancer.  Health equity was the major theme of the 2021 meeting, held June 4-8, 2021, and multiple studies showed that there are many disparities in lung cancer care that need to be addressed by our community.  For instance, in data presented by the U.S. Food and Drug Administration, Black patients only made up 2% of the participants on the lung cancer clinical trials leading to immunotherapy drug approvals. The meeting made it clear that at all levels – from medical education through delivery of care – there are gender, racial/ethnic, and socio-economic disparities that need to be addressed to ensure high quality cancer care for everyone.   

Some of the research highlights of the meeting were:  

Targeted Therapies  

EGFR 
  • A number of studies looked at treatment options for patients that have had progression while taking osimertinib (Tagrisso), the current standard of care for newly diagnosed patients with an EGFR mutation. Among the drugs showing promise are: 
    • The combination of Rybrevant (amivantamab) and lazertinib given in the CHRYSALIS trial to patients who had not yet received further treatment after Tagrisso. 
    • Patritumab deruxtecan (HER3-DXd) which has started being given to patients in early clinical trials after progression while being treated with Tagrisso – even if they had received another treatment like chemotherapy. 
  • Promising data was also presented on drugs targeting rarer EGFR exon 20 mutations, against which traditional EGFR targeted therapy does not work well, including: 
    • Mobocertinib, which was given in a clinical trial to patients who received other treatment before the trial, including some with brain metastasis. 
    • DZD9008, which in the WU-KONG clinical trials was given to patients who had received other treatment prior to joining. 
  • Clinical trial results comparing aumolertinib with gefitinib (Iressa) indicate that it is a better first line option than the already approved Iressa. This is of particular importance for patients who do not have access to osimertinib (Tagrisso) for their first line treatment. 
KRAS 
  • Data presented from the CODEBREAK 100 trial showed that sotorasib (Lumakras) increased overall survival for patients with a KRAS G12C mutation. Sotorasib (Lumakras) was approved by the FDA in May to treat non-small cell lung cancer with a KRAS G12C mutation. [Also see our recent recap of treating KRAS mutated NSCLC.] 
HER2 
  • New updates to the NCCN guidelines, for treatment of patients with a HER2 mutation, have been made to reflect the results of recent clinical trials indicating these patients could benefit from Enhertu (trastuzumab deruxtecan) or Kadcycla (ado-trastuzumab emtansine) if they have progression on chemotherapy as a first treatment, which is still the standard of care. 
Other Mutations 
  • Longer-term updates of the clinical trials that resulted in the approval of the RET targeted therapies Retevmo (selpercatinib) and Gavreto (pralsetinib) continued to show good results. 
  • In addition to those mentioned above there were several early-stage trials that looked at targeted therapies for mutations that do not currently have one. These included targeted therapies for PARP7, NRG1, SHP2, and GLS1. 

Biomarker Testing  

  • Receiving comprehensive biomarker testing is an important part of making treatment decisions for non-small cell lung cancer patients, especially as the number of biomarkers and approved targeted therapies keeps increasing.  However, data from the MYLUNG Consortium, and the Flatiron health records data demonstrated that significant testing gaps still exist:  
    • While a majority of patients in the US are receiving some biomarker testing, most are not being tested for every biomarker with an approved targeted therapy.  
    • Black lung cancer patients are receiving biomarker testing at lower rates then white patients, despite having the same rate of targetable mutations.  

Immunotherapy for Metastatic Non-Small Cell Lung Cancer  

  • Several studies presented at the meeting provided further evidence of the effectiveness of current FDA approved immunotherapy treatments. 
    • For patients with PD-L1 levels of less <50%, an FDA analysis of clinical trials indicated, that chemotherapy/immunotherapy combination therapy remains the best first treatment option. 
    • A 2-year update from the CHECKMATE 9LA Trial indicated that patients treated with the combination of nivolumab (Opdivo), ipilimumab (Yervoy), and chemotherapy, continued to have increased survival compared to chemotherapy treatment alone. 

For Earlier Stages of Non-Small Cell Lung Cancer 

  • Multiple studies looked at giving different kinds of treatments after surgery (“adjuvant treatment”) to improve outcomes.  
    • The IMPower010 trial showed that adding Tecentriq (atezolizumab) after surgery and chemotherapy could improve “Disease Free Survival” (the amount of time before cancer recurs) in patients with Stage 2 and 3 lung cancer – particularly if they had the PD-L1 biomarker (>1%). The study is ongoing to understand if it improves survival outcomes. 
    • Chemotherapy, which was given in many trials alone or together with other drugs after surgery, continued to show benefit as a standard part of adjuvant treatment. 
  • Studies also explored which treatment were best for patients who cannot receive surgery. Updated data from the PACIFIC trial confirmed that adding Imfinzi (durvalumab) after chemotherapy and radiation for Stage III NSCLC improves survival. After 5 years, a third of patients who took the durvalumab regimen were still disease-free. 
  • There was also research on what treatments would be best given BEFORE surgery to improve outcomes – importantly, one study showed that an EGFR targeted therapy given before surgery did not decrease the usefulness of EGFR targeted therapy if you needed to take it later in your treatment. 
  • Several studies also looked at the best ways to use radiation to treat early stage lung cancer. Among the findings were: 
    • SABR (stereotactic ablative radiotherapy) was not worse than surgery for treating operable stage I lung cancer and both could be valid choices to discuss with your doctor. 
    • SABR should be used at lower doses to treat inoperable tumors touching the main bronchus, trachea or esophagus to avoid increased toxicity. 
    • Radiation therapy after surgery did not have a survival benefit for stage III NSCLC that could be operated on. 
  • Several studies also looked at using circulating tumor DNA (ctDNA) as a tool to tell which patients would get the most benefit from treatment before surgery and to find remaining cancer cells after treatment before they could be seen on scans. 

Small Cell Lung Cancer (SCLC) 

  • Negative trials are important too! One trial showed that a higher dose of radiation once a day was NOT better (based on survival and side effects) than a standard dose of radiation twice per day.  
  • Early data was presented on the new drug tarlatamab that targets DLL3 to find the right dose of the drug. Some participants had good responses to the drug and we expect to see more clinical trials in the future.  
  • Studies continue looking at the biology of SCLC and future biomarkers that could be used in the treatment of small cell. Many promising leads are developing.  

For more in-depth summaries and insights about the research presented at ASCO 2021, tune into the Lung Cancer Living Room – Best of ASCO Edition on July 20 and look out for the July edition of the Magnifying Lens newsletter.