More effective combinations of targeted therapies, strategies to minimize side effects, the use of subcutaneous rather than intravenous immunotherapies, and artificial intelligence (AI) tools to better predict responses to immunotherapy are among the latest advances.
At the European Lung Cancer Congress 2025, held in Paris, France, by the European Society for Medical Oncology, numerous clinical trials unveiled new avenues to improve the survival and quality of life of patients with metastatic lung cancer.
Step-by-Step Progress
Each year, 50,000 new lung cancer cases are diagnosed in France, with non–small cell lung cancer (NSCLC) accounting for 80% of these cases.
More than two thirds of lung tumors are diagnosed at the metastatic stage, making them inoperable. Despite the poor prognosis, the average 5-year survival rate has doubled from 10% to 20% over the past two decades, indicating steady, incremental progress.
“There is no single type of lung cancer; there are many different types identified, notably by their genetic markers,” explained Nicolas Girard, MD, PhD, thoracic oncologist at the Institut Curie in Paris, France, during a press conference at the congress. These tumors carry various mutations, including EGFR, KRAS, ALK, BRAF, and HER2 mutations. In France, 100% of NSCLCs benefit from genetic analysis to identify mutations that may be treatable with targeted therapies.
Among the major advances presented at the congress were the findings from the international MARIPOSA phase 3 trial, which evaluated not only a single targeted therapy but also a combination of two targeted therapies against lung tumors with an EGFR gene mutation, showing a significant advancement.
“For patients with this mutation, which affects 20% of cases, targeted therapies are available, he said. Most patients respond well, with tumor shrinkage and improved survival,” Girard emphasized.
“However, after an average of 18 months, these medications tend to lose their effectiveness. This trial showed that a dual-targeted approach is significantly more effective than using a single drug.”
The MARIPOSA trial, involving more than 1000 patients, compared the survival outcomes of amivantamab combined with lazertinib, both drugs targeting the EGFR mutation, with those of osimertinib alone, a standard anti-EGFR therapy.
“The results revealed that after 3 years, 60% of patients receiving the combination therapy were still alive compared with 51% with monotherapy. After 42 months, the gap widened further, with survival rates of 56% and 44%, respectively,” said the study co-author Enriqueta Felip, MD, PhD, head of the Thoracic Cancer Group within the Oncology Department of the Vall d'Hebron University Hospital, Barcelona, Spain.
Anti-EGFR–targeted therapy alone now is surpassed by the combination of the two treatments in this indication. “A request has been submitted to the transparency commission for such a combination to be available in France. In the near future, these dual combinations could be paired with other molecules, such as antibody-drug conjugates, as trials have also shown promising results with such combinations,” Girard said.
As part of the MARIPOSA trial, the randomized COCOON study, led by Girard, investigated strategies to prevent the more significant side effects associated with dual anti-EGFR therapy. The trial evaluated the effectiveness of prophylactic interventions such as oral antibiotics, topical skin moisturizers, scalp lotions, and other local skin care measures.
According to Pascale Tomasini, MD, oncologist and lung expert at Assistance Publique Hôpitaux de Marseille in Marseille, France, who also participated in this trial, this approach reduces the incidence and severity of skin-related side effects by 70%. Therefore, it is possible to intensify targeted therapy while minimizing toxicity.
At this congress, other preliminary trials of targeted treatments also showed promising results in lung cancers with KRAS mutations, which account for 29% of cases. Similarly, new data from the multicenter phase 1/2 SOHO-01 trial involving a HER2 inhibitor targeting 3% of NSCLCs driven by this mutation were described as highly encouraging.
In the field of immunotherapy, which is indicated for certain types of lung cancer, recent studies have identified new strategies to differentiate between likely responders and nonresponders. Although only 30% of patients benefit from immunotherapy, predicting who will respond remains challenging. Researchers from Institut Curie, Inserm, and Mines Paris-PSL have combined multiple data types — genomic, radiomic, histopathologic, and clinical — within AI algorithms. Their findings suggest that combining all four data types significantly improves the ability to predict treatment responses.
Another key advance concerns patients with operable lung cancer. French researchers have confirmed the findings of the CheckMate 816 study in real-world settings; three doses of immunotherapy before surgery improved response rates and reduced the risk for death and long-term recurrence by 40%.
Finally, immunotherapy can be administered subcutaneously in lung cancer. Clinical trials have shown that this route of administration is equally effective as the intravenous route. Patients can now be treated at home instead of receiving infusions at the hospital. This is another small victory for the quality of life of patients.
This story was translated from Medscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.