The 2020 American Society of Clinical Oncology (ASCO) Annual Scientific Program went virtual for the very first time in an unprecedented year for both the world and for lung cancer research. A timely six new FDA approvals came out right before ASCO, paving the way for a rich discussion and reasons to look forward to future progress. Below are some of the major highlights from ASCO 2020 and what the future holds for lung cancer research.
Non-small cell lung cancer
The much anticipated abstract and discussion of the ADAURA trial was presented by LCRF Scientific Advisory Board (SAB) member Dr. Roy S. Herbst and his colleagues. The ADAURA trial was a phase III trial looking at the efficacy of osimertinib (Tagrisso) as an adjuvant targeted treatment for early stage NSCLC patients with the EGFR mutation with or without standard chemotherapy treatment. The trial ended the double-blinded study design earlier than expected due to evidence that Osimertinib provides a 79% reduction in risk of disease or recurrence of disease. This trial is the first evidence in research showing a benefit to adding targeted therapy to the existing standard of care for this particular lung cancer patient group.
The GEOMETRY mono-1 trial presented at ASCO highlighted the ground-breaking work that went behind last month’s FDA approval of capmatinib (Tabrecta). Capmatinib is currently approved to treat NSCLC patients with the MET exon 14 mutation. The trial showed evidence that capmatinib can be used in both previously treated and treatment naïve patient groups with favorable safety profiles. Capmatinib is the first ever targeted therapy approved to treat the MET exon 14 mutation.
The LIBRETTO-001 trial presented another brand new targeted therapy for the RET mutation recently FDA approved. Selpercatinib (LOXO-292) used to treat NSCLC patients with the RET mutation showed significant disease improvement and tolerability, regardless of prior treatment. Two more targeted therapies are being studied and up for possible FDA approval to treat the RET mutation as well. An abstract by LCRF grantee Dr. Alexander Drilon and colleagues on the ARROW trial show promising evidence for TPX-0046 for a RET treatment. Out of the same ARROW trial, pralsetinib (BLU-667) was presented on, which showed successful treatment results for solid tumors containing the RET mutation.
There is much left to discover in the treatment space for lung cancer patients who do not respond well to immunotherapy or targeted therapy. An abstract presented at ASCO by LCRF grantee Dr. Diane Tseng and colleagues explored pathways to enhancing the immune system’s response to cancer cells. This work paves the way for better understanding how T cells can be mapped for use in lung cancer treatment.
Efforts continue to identify targeted treatment for NSCLC patients with the KRAS mutation, which occurs in upwards of 30% of all NSCLC patients. An abstract presented by LCRF grantees Dr. Kathryn Arbour, Dr. Mark Kris, Dr. Charles Rudin, and their colleagues shows promising results of an early phase clinical trial examining the use of a KRAS-G12C mutation (occurs in 12% of NSCLC patients) therapy. This is currently being compared to chemotherapy and immunotherapy to identify efficacy for this significantly large NSCLC patient group.
Small cell lung cancer
In 2018 the first ever immunotherapy treatment (nivolumab) was approved by the FDA for SCLC, a rare and aggressive type of lung cancer that hasn’t seen a new treatment approval in over a decade. Since then, researchers have been working diligently to examine adjuvant treatments for SCLC.
At ASCO 2020, LCRF SAB member Dr. Suresh Ramalingam and colleagues presented their abstract on the use of nivolumab (Opdivo) in combination with chemotherapy for the first-line treatment of extensive-stage SCLC. Their study showed that the addition of nivolumab provided a significant benefit without any additional safety issues. Nivolumab was originally FDA approved only as a third-line treatment for SCLC.
Proving similar, the KEYNOTE-604 trial was presented by LCRF SAB member Dr. Charles Rudin and his colleagues, on the addition of pembrolizumab (Keytruda) to chemotherapy treatment as a first-line treatment for extensive-stage SCLC. The combined use of pembrolizumab plus chemotherapy showed prolonged overall survival versus chemotherapy alone.
Looking ahead to the future of lung cancer research
ASCO 2020 highlighted the blossoming diversification of lung cancer treatment options. As we begin to understand more about biomarkers (mutations) we will continue to see progress on the identification of personalized treatments. Historically, lung cancer was seen as a homogenous group with no differentiation between patient groups within. The advent of personalized medicine has completely changed the way we think about lung cancer. More than ever we are identifying the unique patient groups within the lung cancer space. Research exploring the adjuvant treatment setting will continue to thrive and identify the safest and most effective combinations of treatment.
ASCO abstract sources:
- Abstract #3087 Diane Tseng, Stanford – Discovery of a novel shared tumor antigen in human lung cancer
- Abstract Dr. Roy Herbst – Osimertinib as adjuvant therapy in patients (pts) with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA
- Abstract – FDA approved selpercatinib for RET
- Abstract – ARROW RET mutation pralsetinib tx trial ongoing
- Abstract Dr. Suresh Ramalingam – nivolumab for 1st line ES-SCLC
- Abstract Dr. Charles Rudin – pembro + chemo for 1st line ES-SCLC
- Abstract – GEOMETRY trial with capmatinib for NSCLC MET
- Abstract Dr. Alex Drilon – RET new drug TPX0046
- Abstract Dr. Kathryn Arbour, Dr. Mark Kris, Dr. Charles Rudin – KRAS G12C mutation therapy abstract