Research Highlights
Since our last newsletter, the European Society for Medical Oncology (ESMO) held their annual conference in Madrid in October. Several “practice changing” research findings were announced with regards to EGFR treatments, which we will summarise for you here.
1. The PAPILLON (Phase 3) study investigating the effectiveness of Amivantamab + Chemo versus Chemo alone as a first line treatment for Exon 20 EGFR patients. This study showed that almost 50% of patients on the combination treatment had not progressed after 12 months, compared to only 13% on chemo alone. By 18 months, 31% were still stable compared to only 3% in the chemo only group. This means that progression-free survival (which is the length of time patients were on the treatment until progression was detected) was significantly longer for patients on Amivantamab + Chemo versus Chemo alone. Furthermore, a higher proportion of patients responded to the combination therapy (objective response rate =73%) compared to those on chemo alone (47%).
2. Another study also looked at the effectiveness of Amivantamab, this time in patients with common Exon 19 deletions or Exon 21 L858R mutations. The MARIPOSA (Phase 3) trial compared three different groups in a first-line setting: one that received Osimertinib (the current standard of care in the UK), one that received Lazertinib alone, and another that received a combination of Amivantamab + Lazertinib. They found that while Osimertinib and Lazertinib alone performed similarly, patients given the combination treatment performed best with almost 50% of all patients still stable at 24 months (compared to 34% on Osimertinib alone). The average duration of response to treatment was 25.8 months for the combined treatment, compared to 16.8 months for Osi alone. Overall, these results suggest that a combination of Amivantamab + Lazertinib may be more effective as a first line treatment than Osimertinib, with better response rates and longer progression-free survival times.
3. The MARIPOSA-2 trial also looked at patients with Exon 19 deletions or Exon 21 L858R mutations, but this time looked at patients who had previously been treated with Osimertinib. As we know that tumours often develop a resistance to Osimertinib over time, identifying possible treatment options that can follow this drug is really important. This study compared three different type of treatment: Chemotherapy alone (which is standard of care in the UK after progression on Osi), Chemotherapy + Amivantamab, and Chemotherapy + Amivantamab + Lazertinib. They found that a similar proportion of patients responded well to the combination treatments (~63-64%), which was almost double the number of patients who responded to chemotherapy alone (~36%). What’s more, more than 50% of patients had not progressed on either combination treatment after 6 months, compared to only 30% on chemo alone. An unexpected finding of this study was that the combination therapies appeared to exhibit some brain penetration. Average progression-free survival for patients with brain metastases was similar for the combination therapies (12.5 months for Chemotherapy + Amivantamab and 12.8 months for Chemotherapy + Amivantamab + Lazertinib), compared to 8.3 months for patients on Chemotherapy alone.
The above 3 trials all show the possible usefulness of Amivantamab as a treatment option for EGFR patients with both common and uncommon (Exon 20) mutations. However, when it comes to this drug, it is worth noting that its use is associated with some significant toxicities (including blood clots, skin reactions, paronychia - finger and toenail infections). So if this is a drug you are thinking of, make sure to talk all of this through with your oncology team. While Amivantamab isn’t currently available on the NHS, but it can be accessed via private and self-funding routes. Furthermore, given the significance of the above trial results, we would expect to see Janssen (the manufacturers) applying for a license to use Amivantamab in the ways explored above soon. We will keep you updated on any NICE approval applications in the future.
4. A further study that was presented at ESMO, was the phase II RAMOSE trial which looked at the potential benefits of adding the drug Ramucirumab (which is a type of drug known as a VEGFR2 antagonist) to Osimertinib. After 12 months, over 75% of patients on the combination treatment had not progressed; compared to 62% on Osimertinib alone. The median time to progression was significantly longer for patients on the combination treatment, compared to 15.6 months with Osimertinib alone. These longer progression-free survival times on the combination treatment were seen in EGFR-mutant NSCLC patients both with and without brain metastases.
5. In a previous newsletter we brought you the results from the ADURA trial which showed that 85% of patients with operable EGFR non-small cell lung cancer (with Ex19del or L858R) who received Osimertinib following a lung resection were still alive after 5 years, and had an average progression free survival of nearly 5 and a half years. Based on these findings, Astra Zeneca are applying for this treatment to be available on the NHS, and are currently going through the NICE approval processes (more information HERE). We will bring you updates on this as we are able, but in the meantime, if this is a treatment option you would like to explore, Osimertinib is currently available through the Cancer Drugs Fund following tumour resection in adults with stage 1b to 3a disease.
Current research
We also wanted to let you know about a couple of studies that are currently underway with EGFR patients. Firstly, the RAMON study is investigating the potential advantages of using radical treatment for patients with metastatic lung cancer (Stage 4). Radical treatment can involve surgery, radiotherapy or ablation – which options are used will be decided by the trial doctors. As part of this Phase 3 study, participants will either receive radical treatment alongside their systemic treatment (which might be chemo, or TKIs); or systemic treatment alone. If you would like to find out more about this study, click HERE or contact the Ramon study team to find out more.
We are also carrying out our own research into the wellbeing of patients with mutation driven lung cancer. We all know that being diagnosed with a mutation driven lung cancer can be incredibly stressful and overwhelming. However, there is very little research into the wellbeing needs for these patients and their families. As such, in partnership with the ALK Positive UK, the Ruth Strauss Foundation and the Open University, we are holding another Wellbeing and Research Event, this time in Manchester on March 16th. The aim of this research is to find out more about patient experiences, so we can provide better support to patients after diagnosis. We also want to explore the possibility of developing an online support program or resource, dedicated to lung cancer patients. To do this, we want to talk to patients and their families to explore several questions around wellbeing and support. If you would like to find out more about this research, or sign up to take part, please visit HERE by March 6th. We would love to see as many of you as possible at this event!
By Gini Harrison, Research Trustee
References
1. 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.
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. Passaro, A., Cho, B. C., Wang, Y., Melosky, B., Califano, R., Lee, S. H., ... & Wang, J. (2023). LBA15 Amivantamab plus chemotherapy (with or without lazertinib) vs chemotherapy in EGFR-mutated advanced NSCLC after progression on osimertinib: MARIPOSA-2, a phase III, global, randomized, controlled trial. Annals of Oncology, 34, S1307.
4. Le, X., Patel, J., Shum, E., Sanborn, R. E., Baik, C. S., Shu, C. A., ... & Saltos, A. (2023). LBA71 A multi-centre open-label randomized phase II study of osimertinib with and without ramucirumab in TKI-naïve EGFR-mutant metastatic NSCLC (RAMOSE trial interim analysis). Annals of Oncology, 34, S1313-S1314.
5. Tsuboi, M., Herbst, R. S., John, T., Kato, T., Majem, M., Grohé, C., Wang, J., Goldman, J. W., Lu, S., Su, W. C., de Marinis, F., Shepherd, F. A., Lee, K. H., Le, N. T., Dechaphunkul, A., Kowalski, D., Poole, L., Bolanos, A., Rukazenkov, Y., Wu, Y. L., … ADAURA Investigators (2023). Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. The New England journal of medicine, 10.1056/NEJMoa2304594.