Inaugurated by Andrés Cervantes (Valencia, Spain), President of the European Society for Medical Oncology (ESMO) and ESMO Congress 2023, this year’s annual meeting, celebrated in Madrid, 20-24 October, included 2,546 abstracts accepted for presentation, including 108 late-breaking abstracts. During the Opening Session, Scientific Chair Silke Gillessen (Bellizona, Switzerland) heralded ESMO Congress 2023 as “the year of the lung cancer abstracts”.
Gearing up to this year’s Congress, an ESMO press release promised exciting advances in first-line treatment for patients with non-small cell lung cancer, “More people with non-small cell lung cancer (NSCLC) are likely to benefit from new drugs that target molecular alterations in tumor cells, with less need for chemotherapy, following results of multiple landmark clinical trials reported for the first time in late-breaking presentations at the ESMO Congress 2023.”
“Making headlines during the meeting, potentially practice-changing data from several studies reported improved outcomes versus standard of care in patients with both early and late-stage NSCLC, achieved through combinations of novel, experimental therapies targeting both common and rare tumor cell mutations,” observes Enriqueta Felip, Principal Investigator of the Vall d’Hebron Institute of Oncology’s (VHIO) Thoracic Tumors Group and Head of Section at the Vall d’Hebron University Hospital’s (HUVH) Medical Oncology Department.
Just some of these studies included late-breaking data from the global phase III MARIPOSA, MARIPOSA-2 and PAPILLON trials, and the phase II DELLphi-301 study.
The promise of novel drug combinations in advanced or metastatic EGFR-mutated NSCLC
Primary results of MARIPOSA, presented by first author Byoung Chul Cho at the Yonsei Cancer Center (Seoul, Korea, Republic of Korea) during Presidential Session 3 (1), support first-line treatment with amivantamab, an EGFR-MET bispecific antibody with immune-cell directing activity, plus third generation EGFR tyrosine kinase inhibitor lazertinib as the new standard of care in treatment naïve patients with EGFR-mutated locally advanced or metastatic NSCLC.
Designed to evaluate the efficacy of this novel drug combination versus current standard of care with osimertinib targeted therapy, this controlled phase III study included a total of 1074 patients who were randomized 2:2:1 to amivantamab with lazertinib, osimertinib, or lazertinib. At a median follow-up of 22 months, the amivantamab-lazertinib combo showed a 30% reduction in the risk for disease progression or death versus osimertinib, with progression free survival (PFS) of 23.7 months and 16.6 months, respectively.
“Overall survival analysis showed a trend favoring the combination of amivantamab and lazertinib compared to osimertinib. While subsequent follow-up analyses will be required to determine the statistical and clinical significance of OS, our data demonstrate the promise of this novel combination as a future standard of care,” concludes Enriqueta Felip, a co-author of this pivotal study.
Presented by lead author Antonio Passaro at the European Institute of Oncology, IRCCS (Milan Italy), also during Presidential Session 3 (2), results of the MARIPOSA-2 study—published concomitantly in ESMO’s flagship journal Annals of Oncology (3)—point to a new drug combination for the treatment of patients with EGFR-mutated advanced NSCLC after disease progression on standard treatment with osimertinib. This phase III randomized, controlled trial was designed to compare amivantamab plus chemotherapy (with our without lazertinib) versus chemotherapy alone. 675 patients were randomized 2:2:1 to amivantamab with lazertinib plus chemotherapy, chemotherapy, or amivantamab and chemotherapy combined.
At a median follow-up of 8.7 months, PFS significantly improved with the doublet and triplet combinations compared to chemotherapy, with a median PFS of 6.3, 8.3, and 4.2 months, respectively. Median intracranial PFS was 12.5 months for amivantamab combined with chemotherapy, 12.8 months for amivantamab plus lazertinib and chemotherapy, and 8.3 months for chemotherapy. While longer follow-up is required, these data signpost a change in clinical practice for this subgroup of NSCLC patients.
Results of studies including MARIPOSA and MARIPOSA 2 not only demonstrate the promise of new drug combinations for the first-line treatment of NSCLC patients with targetable tumor cell alterations, but also underscore the importance of tumor testing at diagnosis.
“NSCLC is responsible for approximately eight out of ten lung cancer cases. We must therefore continue to collectively advance precision medicine by identifying the most effective combination of targeted therapy, or chemotherapy with immune-based strategies for each individual patient,” concludes Enriqueta Felip.
In addition to these two landmark studies, new data from the randomized, open-label, international phase III PAPILLON clinical trial—presented in an ESMO Presidential Symposium (3) by lead investigator Nicolas Girard, Institute Curie, Institut du Thorax Curie-Montsouris (Paris, France)—simultaneously published in The New England Journal of Medicine (5), co-authored by Enriqueta Felip.
This study was designed to assess the combination of amivantamab and chemotherapy versus chemotherapy alone as first-line treatment for patients with previously untreated advanced, EGFR exon 20 insertion-positive NSCLC. Amivantamab has been approved for the treatment of patient with EGFR exon 20 insertion-positive NSCLC who have had disease progression during or after chemotherapy.
“Considering the immune-cell directing activity of this EGFR-MET bispecific antibody, we hypothesized that the addition of chemotherapy could lead to improved outcomes in this patient population,” observes Felip.
Based on previous results from a phase I study which showed a favorable safety profile and encouraging antitumor activity in a small population of 20 patients, this present study included a total of 308 patients who were randomly assigned 1:1 to receive amivantamab plus chemotherapy, or chemotherapy alone.
Findings show that PFS was significantly longer in the amivantamab-chemotherapy group than in the chemotherapy group, with a median of 11.4 months versus 6.7 months, respectively. At 18 months, PFS was reported in 31% of the patients who received the combination compared to 3% in patients receiving chemotherapy alone. A complete or partial response at data cutoff was reported in 73% and 47% of patients, respectively.
The safety profile of the combination was consistent with the individual agents, and the predominant adverse events associated with amivantamab–chemotherapy were reversible hematologic and EGFR-related toxic effects; 7% of patients discontinued amivantamab owing to adverse reactions.
“These data support amivantamab plus chemotherapy as a new standard-of-care for the first-line treatment of these patients, upon evaluation by the different regulatory authorities and healthcare reimbursement systems,” concludes Enriqueta Felip.
Targeted immunotherapy shows encouraging antitumor activity in patients with SCLC
Presented at an ESMO Congress 2023 Proffered Paper Session as a late-breaking oral presentation (6) by lead author Luis Paz-Ares, Hospital Universitario 12 de Octubre, Madrid, Spain, results from the global phase II DeLLphi-301 clinical trial show the promise of targeted immunotherapy tarlatamb in patients with advanced small-cell lung cancer (SCLC) who had failed two or more prior lines of therapy. This study assessed the efficacy and safety of this novel therapy, with the primary endpoint of objective response (complete or partial response).
Published in parallel in The New England Journal of Medicine (7), data show that tarlatamab, an investigational bispecific T-cell engager (BiTE) immunotherapy, demonstrated antitumor activity with durable objective responses and promising survival outcomes in this patient population, with no new safety signals observed compared to a phase I study.
Overall, 220 patients received tarlatamab. The intention-to-treat group included 100 patients at the selected 10 mg dose. With a median follow-up of 10.6 months, an objective response was observed in 40% of these patients. The median progression-free survival was 4.9 months and median overall survival was 14.3 months. Among those patients who responded to treatment at 10 mg dose, 59% experienced at least six months of response, and objective responses at the time of data cutoff were ongoing in 55% of these patients.
“Comprising 15% of lung cancer cases, small cell lung cancer is a very aggressive type of cancer with an overall 5-year survival rate of 7%. Despite initial high responses to first-line chemotherapy, these patients develop resistance to second-line and subsequent therapies and face a dire prognosis,” observes Enriqueta Felip, co-author of this present study.
“Demonstrating a favorable benefit-risk ratio with no new safety signals, results of this study support the use of tarlatamab targeted immunotherapy in the third-line treatment of SCLC and represent an important advance toward improving outcomes in this patient population,” concludes Enriqueta Felip, co-Director of Clinical Research at VHIO and President of the Spanish Society of Medical Oncology (SEOM).
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References:
Presidential 3
Date: 23.10.2023
Time: 16:30 – 18:15h
Chairs: Fabrice André (Villejuif, France) Karin Jordan (Potsdam, Germany)
Room: Madrid Auditorium – Hall 6
Session Type: Proffered Paper Session
Speaker: Byoung Chul Cho (Seoul, Korea, Republic of Korea)
Presidential 3
Date: 23.10.2023
Time: 16:30 – 18:15h
Chairs: Fabrice André (Villejuif, France) Karin Jordan (Potsdam, Germany)
Room: Madrid Auditorium – Hall 6
Session Type: Proffered Paper Session
Speaker: Antonio Passaro (Milan, Italy)
Presidential 1
Date: Sat, 21.10.2023
Hora: 16:30 – 18:15h
Chairs: Solange Peters (Lausanne, Switzerland) Jean-Yves Blay (Lyon, France)
Room: Madrid Auditorium – Hall 6
Session Type: Proffered Paper Session
Speaker: Nicolas Girard (Paris, France)
Proffered Paper Session
Date: 20.10.2023
Time: 14:00 – 15:45h
Chairs: Rafal Dziadziuszko (Gdansk, Poland) Fiona Blackhall (Manchester, United Kingdom)
Room: Sevilla Auditorium – Hall 9
Speaker: Luis Paz-Ares (Madrid, Spain)
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