The European Society for Medical Oncology (ESMO) recently held its annual conference from October 20 – 24, 2023 in Madrid, Spain. ESMO represents one of the largest gatherings of the international oncology community, and this year’s meeting had over 30,000 registered attendees from around the world.
Though October 19th brought record rainfall to Madrid, breaking a 100-year record, the rain in Spain didn’t dampen the palpable excitement of this year’s meeting. This was an especially exciting ESMO because there were a number of important lung cancer presentations that represent practice-changing advances for the field. Below is a brief summary of the findings from several lung cancer trials reported at the conference.
Targeted Therapy
ALINA: This trial looked at the use of an ALK-targeted drug, alectinib, in the adjuvant setting (after surgery) in patients with early-stage lung cancer. Compared to platinum-based chemotherapy alone, alectinib showed significant improvement in disease-free survival in patients diagnosed with stage IB – IIIA ALK-positive non-small cell lung cancer (NSCLC). Researchers are still waiting to see if the use of alectinib improves overall survival in this population but based on the findings of the trial thus far, these results are game-changing for patients with early-stage disease who are carrying this biomarker.
LIBRETTO-431: This trial reported positive results for the use of the RET-targeted drug, selpercatinib, compared to chemotherapy plus or minus immunotherapy in patients with RET fusion-positive advanced NSCLC, showing both prolonged progression-free survival and delayed onset of central nervous system progression and may even be protective against brain metastases. Based on these data, selpercatinib is now recommended as an upfront treatment in patients diagnosed with RET-positive NSCLC.
MARIPOSA and MARIPOSA-2: These trials evaluated new approaches for the management of EGFR-positive (exon 19del and L858R) NSCLC, where drug resistance is common in patients treated with the current standard of care, osimertinib. In the MARIPOSA trial, investigators evaluated the combination of amivantamab, an EGFR-MET bispecific antibody, and lazertinib, a third-generation EGFR tyroskine kinase inhibitor (TKI), compared to osimertinib alone in patients with EGFR-positive NSCLC and found a 30% reduction in disease progression or death in patients receiving the combination of two drugs. In the MARIPOSA-2 trial, investigators looked at the use of these drugs in the second-line setting, comparing amivantamab plus chemotherapy or amivantamab plus lazertinib plus chemotherapy to chemotherapy alone. Both amivantamab regimens led to improvements in progression-free survival and overall response rate. However, both trials saw increased rates of adverse events and toxicities, which will have to be taken into consideration for patients and providers deciding on the best treatment plan. Additionally, amivantamab must be administered intravenously, whereas osimertinib can be taken by mouth.
PAPILLON: Amivantamab plus chemotherapy was also compared to chemotherapy alone for the treatment of NSCLC containing the EGFR exon 20 insertion. As with the other EGFR mutations described above, the use of amivantamab in addition to chemotherapy led to an increase in progression free survival compared to chemotherapy alone, suggesting that this combination can be used in the first-line setting for patients harboring this alteration.
Key takeaways: As we see targeted therapies move into the early-stage NSCLC setting, the above sessions at ESMO23 reinforce the importance of comprehensive biomarker testing for all patients diagnosed with NSCLC, regardless of stage. Additionally, in the context of different options for EGFR-mutated NSCLC, it reinforces the importance of shared decision making between the patient and their provider to weigh the benefits compared to added toxicities and the inclusion of a drug that must be administered intravenously compared to the oral therapies that are the current standard of care.
Immunotherapy
AEGEAN: Perioperative (both preceding and following surgery) durvalumab plus chemotherapy was compared to chemotherapy alone in patients with resectable (removable by surgery) NSCLC. Specifically, patients receiving durvalumab plus chemotherapy prior to surgery followed by durvalumab after surgery had better outcomes (such as event-free survival and pathological complete response) than patients getting chemotherapy alone prior to surgery. This study suggests that an immunotherapy treatment (such as durvalumab) before and after surgery for NSCLC leads to improved outcomes.
CHECKMATE 77T: In another evaluation of immunotherapy in the perioperative setting (both preceding and following surgery), the combination of nivolumab plus chemotherapy before surgery followed by nivolumab after surgery in patients with resectable NSCLC resulted in improved event-free survival compared to chemotherapy and placebo following surgery.
KEYNOTE 671: This trial evaluated perioperative pembrolizumab, an immunotherapy drug, with neoadjuvant chemotherapy before surgery. The combination of immunotherapy both before and after surgery combined with chemotherapy before surgery led to improved overall survival in patients with resectable NSCLC. This is the first neoadjuvant study for resectable lung cancer to see such survival gains since the 1990s, according to study investigator Dr. Jonathan Spicer.
TROPION: This trial evaluated datopotamab deruxtecan, a TROP2-directed antibody drug conjugate, compared to docetaxel, a standard chemotherapy, in patients with advanced, pre-treated NSCLC, including patients with targetable alterations including ALK, EGFR, MET exon 14 skipping, NTRK, RET and ROS1. Overall survival data are still being evaluated though there is a suggestion of improved overall survival that does not yet meet statistical significance.
Key takeaways: As with targeted therapies outlined above, we are now seeing immunotherapy move into the early-stage setting, where it is being used both before and after surgery for patients whose tumors are resectable. We also expect to see more progress with antibody drug conjugates in the future.
Beyond attending the exciting conference presentations, the LUNGevity team also had a strong presence during and preceding the European Society for Medical Oncology meeting. Members of the policy team, including Drs. Elizabeth (Libby) Barksdale and Tod Guidry, hosted a Scientific and Clinical Roundtable, where they met with key stakeholders to understand some of the drivers and barriers to clinical trial participation in Europe, including recent regulations that may impact trial access.
LUNGevity’s CEO, Andrea Ferris, and I participated in industry symposia on topics including how to expand the impact of precision oncology and issues related to lung cancer diagnosis, including the benefits of tissue versus liquid (blood) biopsy. Prior to the start of ESMO, I also gave an invited talk at the European Alliance of Personalised Medicine Presidency Conference, which focused on “Making Access to Personalised Medicine a Reality for Patients.”
In addition, I attended an advocacy reception hosted by the Workgroup of European Cancer Patient Advocacy Networks, where I had the privilege of interacting with fellow advocates from Lung Cancer Europe, ALK International, the ROS1ders, EGFR Resisters and KRAS Kickers.
From the exciting scientific progress to the opportunities to share LUNGevity’s thought leadership with international lung cancer experts and patient advocates, ESMO23 in Madrid was a smashing success. We look forward to next year’s meeting in Barcelona!