Lung cancer: these advances that will change care (ASCO 2024)

Several types of lung cancer

There are mainly two forms of lung cancer depending on the origin of the bronchial cells from which they arise.

• So-called non-small cell lung cancers (NSCLC, 85% of cases with adenocarcinomas, squamous cell carcinomas and large cell carcinomas);
• So-called small cell lung cancers (SCLC, 15% of cases, rarer forms mainly linked to tobacco and very aggressive).

In recent years, the discovery of mutations in lung tumors has enabled the establishment of a molecular classification of bronchial cancers, with some of these mutations making it possible to use targeted therapies.

A new standard for small cell cancers

Concerning small cell cancers that are inoperable but without metastases, a study conducted on nearly 500 patients showed that the addition of immunotherapy after the usual treatments (chemotherapy and radiotherapy) reduces the risk of death by 27%. Average survival increases from 33 months to 56 months. The immunotherapy used is durvalumab, a PD-L1 antibody marketed under the name Imfinzi ® by the Astrazeneca laboratory.

According to the main author of this study called Adriatic¹, this is a real breakthrough in small cell cancer which will make durvalumab a new standard of treatment. More information on this study in our article “Lung cancer: immunotherapy changes the prognosis of patients with a formidable form”.

New for locally advanced EGFR cancers

Another study concerns NSCLCs which present a particular mutation of the EGF receptor known as EGFR type. This represents 10 to 15% of patients in Western countries and 30 to 40% of patients in Asia.². In patients with this type of advanced (stage 3) unresectable cancer whose disease has not progressed during or after platinum-based chemotherapy, a targeted therapy, osimertinib (marketed under the name Tagrisso® by Astrazeneca) has been tested^3.4.

Result: osimertinib significantly improved the time before the disease progressed (progression-free survival – PFS), 39 months for the treated group versus 6 months with the placebo. Fewer brain metastases were also reported (8% versus 29%). Even if data on overall survival are still missing, these very encouraging results could change treatment recommendations. It also remains to be seen whether the reduction in the risk of progression is proportional to the duration of treatment.

Conjugated antibodies constitute a therapeutic class in full development in oncology and which has obtained interesting results against different cancers (see in particular our article “Metastatic breast cancer: a promising drug could limit the use of chemotherapy”). These are chemotherapies coupled with antibodies directed against a protein present on the surface of tumors. This “targeted missile” will thus deliver chemotherapy to the heart of the tumor.

A drug in this class, an anti-TROP2, was used against metastatic NSCLC in therapeutic failure as part of the ICARUS-Lung01 study conducted at Gustave Roussy. This drug targets the TROP molecule on the surface of tumor cells in 80% of lung cancers⁵.

Result: The results highlight a promising response rate of around 26%. In total, a quarter of the patients showed a reduction in lesions of at least 30%. By analyzing the data more precisely, it appears that non-squamous cancers and those carrying the EGFR mutation had the best responses. A real breakthrough for patients who are at a therapeutic impasse and who had already received standard treatments for this disease⁶.

Outstanding results for advanced ALK cancers

Another study concerns NSCLC carrying another type of mutation called ALK present in approximately 3 to 5% of NSCLC. In these patients, lorlatinib (marketed under the name Lorviqua ® by Pfizer) significantly reduced the progression of the disease to an advanced stage and increased the survival rate of patients compared to another treatment, crizotinib. . In detail, 60% of patients who received the new drug (administered in oral form once a day) were still alive without disease progression at 5 years, compared to 8% of patients in the crizotinib group.⁷.

“These long-term results are outstanding and this study confirms the exceptional durable efficacy of lorlatinib as a first-line choice for patients with ALK-positive non-small cell lung cancer” concluded Prof. David R. Spigel, scientific director of the Sarah Cannon Research Institute during the ASCO congress⁸.

Another subgroup of tumors which benefited from progress during this congress: NSCLCs with metastases (cancer spread to other organs) carrying a KRAS G12C mutation (the KRAS mutation is present in 30% of patients and the KRASG12C subgroup in 13%). A targeted therapy adagrazib (marketed under the name Krazati ® by BMS laboratories) has demonstrated interesting results in patients with advanced or metastatic stages already treated with chemotherapy and/or immunotherapy⁹.

The time before the disease progressed again was 5.5 months for treated patients compared to 3.8 months for patients receiving chemotherapy, who had more side effects.¹⁰. Longer term results are necessary but given the absence of therapeutic options for these patients, this compound represents real hope.