Research Highlights May 2024

Since our last newsletter, the British Thoracic Oncology Group (BTOG) held their annual conference in Belfast in April. This conference is an opportunity for lung cancer specialists across the UK (including respiratory physicians, medical oncologists, surgeons, CNSs, academics and more) to come together and share the latest research and best practice. It’s also a chance for patient advocates to learn more about what’s happening in terms of research and possible future treatment options, as well as share information about how best to support the wellbeing of those affected by lung cancer. Two of our Trustees went to represent EGFR+, and have written up the highlights for you here.

One of the key take home messages from the BTOG conference is how important it is to know what your mutation is. EGFR mutations typically fall into three categories: “Common/Classical mutations” - these include Exon 19 and Exon 21 (L585R) mutations; “Exon 20 mutations”; and “Uncommon mutations”. Which mutation type you have often indicates which treatments are most likely to be effective – so it is really important to understand which you have.

Prof Jarushka Naidoo gave a talk, providing an overview of the research into cutting-edge EGFR treatments. These were:

Common Mutations

FLAURA21 - This Phase 3 trial showed that giving Osimertinib in combination with chemotherapy leads to significantly longer progression-free survival (which is the length of time patients are on a treatment until seeing progression) in comparison to Osimertinib alone in patients with Stages IIIB/C or IV EGFR+ lung cancer – lining this treatment combination up as an effective future first line treatment.

MARIPOSA2 – This Phase 3 trial compared the effectiveness of a combination treatment (Amivantamab + Lazertinib), with both Osimertinib and Lazertinib alone. They found that patients who were given the combination treatment had better outcomes (with almost 50% of all patients still stable at 24 months), than patients who were given either Osimertinib or Lazertinib alone (where around 34% were stable at 24 months). While these results suggest that a combination of Amivantamab + Lazertinib may be more effective as a first line treatment, this treatment protocol resulted in significantly more toxicities (including blood clots, skin reactions, paronychia - finger and toenail infections) than the single drugs alone. This combination treatment is due to be considered for appraisal by NICE later this year.

Exon 20 patients

PAPILLON3 – This study investigated the effectiveness of Amivantamab + Chemo versus Chemo alone as a first line treatment for Exon 20 EGFR patients. Those receiving the combination treatment had a significantly longer progression-free survival (with almost 50% stable after 12 months) compared to those on chemo alone. Furthermore, a higher proportion of patients responded to the combination therapy (objective response rate =73%) compared to those on chemo only (47%). This treatment option is due to be considered for appraisal by NICE later this year.

Prof Naidoo also highlighted a pipeline of other potential Exon 20 drugs in the future: Sunvozertinib, Furmonertinib and YK029A.

Uncommon/rare mutations

Uncommon EGFR mutations represent a rare subgroup of NSCLC, and can be split into “classical-like mutations”, or “P-loop and alpha helix compressing (PACC) mutations”. Looking across the research4, PACC mutations generally have better responses to second-generation TKIs (like Afatinib), while more classical-like mutations respond to third-generation TKIs, like (Osimertinib). Specifically, Afatinib is likely to be a good drug of choice for G719X, S768I, E709X, and L747X mutations, whereas for other uncommon mutations such as L861Q, Osimertinib may also have some activity.

Ones to watch

In addition to discussing the results of trials, several avenues of future possible treatment avenues were outlined. These included a Lung Cancer vaccine and a group of drugs known as “antibody drug conjugates”, which can deliver targeted chemo to tumours in a precise manner. The likely effectiveness of both for EGFR lung cancer is currently unknown.

Our research

This year, not only did we go to the conference as charity representatives, but we also presented our own research to the professional lung cancer community. As you may have seen, we have been carrying out research into the wellbeing of patients with mutation driven lung cancer in partnership with the ALK Positive UK, the Ruth Strauss Foundation and the Open University. We presented our preliminary results of this study which found that support needs fell into four key themes: ‘better understanding individual patient conditions/treatment options’, ‘identifying and navigating the existing landscape of support’, ‘supporting condition-related psychological and physical needs (e.g. drug side-effects, scanxiety)’ and ‘peer support and community’. Additionally, eHealth was identified as a possible source of some of this support. You can see a larger image of the poster we presented HERE.

We were also pleased to see a number of other talks and papers that focused on wellbeing – putting the quality of life of lung cancer patients at the forefront of care.

Liquid biopsies

The usefulness of liquid biopsies - that is using a simple blood test to detect cancer cells that have broken away from the tumour and entered the bloodstream - in diagnosis and progression management was also discussed, and generally viewed very favourably. If you are recently diagnosed or experiencing progression, it is worth talking to your oncology team about liquid biopsy as a way to establish what mutation(s) you have, and/or if any new targetable mutations have appeared.

Professor Gini Harrison, Research Trustee

References

1.  Janne, P., Planchard, D., Cheng, Y., Yang, J. H., Yanagitani, N., Kim, S. W., ... & Kobayashi, K. (2023). PL03. 13 osimertinib with/without platinum-based chemotherapy as first-line treatment in patients with EGFRm advanced NSCLC (FLAURA2). Journal of Thoracic Oncology, 18(11), S36-S37.

2.  Cho, B. C., Felip, E., Spira, A. I., Girard, N., Lee, J. S., Lee, S. H., ... & Lu, S. (2023). LBA14 Amivantamab plus lazertinib vs osimertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results from MARIPOSA, a phase III, global, randomized, controlled trial. Annals of Oncology, 34, S1306.

3.  Girard, N., Park, K., Tang, K., Cho, B. C., Paz-Ares, L., Cheng, S., ... & Zhou, C. (2023). LBA5 Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR Exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC): Primary results from PAPILLON, a randomized phase III global study. Annals of Oncology, 34, S1304.

4.  Borgeaud, M., Parikh, K., Banna, G. L., Kim, F., Olivier, T., Le, X., & Addeo, A. (2024). Unveiling the Landscape of Uncommon EGFR Mutations in NSCLC-A Systematic Review. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, S1556-0864(24)00123-0. Advance online publication.