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New treatments against small cell lung cancers were presented at the Chicago Cancer Congress (ASCO 2024). For these non-operable patients but without metastases, the addition of immunotherapy improves patient survival by almost two years.
Small cell lung cancer: rare cancers that are difficult to treat
Depending on the malignant cell causing the disease, we distinguish between non-small cell lung cancer (85% of lung cancer cases) and small cell lung cancer (15% of lung cancer cases). This histological distinction made at the time of diagnosis is essential for choosing the right treatment.
Chosen during a multidisciplinary consultation meeting, in conjunction with the treating physician, the treatment depends on each patient (age, state of health, etc.) and the extent of the disease. When the disease is localized and operable, which is unfortunately rare, the treatment then consists of removal of the tumor by surgery followed by a chemotherapy treatment associated or not with radiotherapy and prophylactic cranial irradiation. In other cases, treatment is based on a combination of chemotherapy associated with radiotherapy, or even prophylactic cranial irradiation. But the prognosis for this cancer remains poor, around 15 to 30% at 5 years.
Studies have suggested that immunotherapy is of interest for these tumors at an early stage or at a metastatic stage. And a study presented as part of the ASCO 2024 World Cancer Congress constitutes real progress for this form of locally advanced cancer and complements treatment that has remained unchanged for more than 20 years.
Nearly 2 years saved with immunotherapy
The study, called ADRIATIC, included 730 patients with limited-stage small cell lung cancer who had completed chemoradiotherapy in the previous 42 days. These are patients whose tumor is too large to be operated on, but no metastases yet. This is an interim analysis comparing outcomes in patients assigned to receive durvalumab (264 patients) with those who received placebo (266 patients).
Durvalumab (marketed under the name Imfinzi by Astrazeneca laboratories) is a so-called anti-PDL1 immunotherapy. Basically, cancer cells escape our immune defenses by expressing proteins on their surface which will block the immune system and prevent it from acting. The antibody then attaches to these blocking molecules and removes the inhibition (in this case the PD-1/PD-L1 pathway). These are called checkpoint inhibitors. Once the blockage is lifted, the immune system resumes its work against the tumor cells. Results as of January 15, 2024:
- Median overall survival was approximately 56 months in patients who received durvalumab and 33 months in patients who received placebo ;
- The median time until the disease progressed again (median progression-free survival – PFS) was approximately 17 months for patients who received durvalumab, compared to 9 months for patients who received placebo.
- The overall survival rate at 36 months was approximately 57% in the durvalumab group and 48% in the placebo group.
- The 24-month PFS rate was approximately 46% in the durvalumab group and 34% in the placebo group.
The rate of serious side effects was the same in both groups (24%): 16% of participants in the durvalumab group stopped treatment due to side effects, compared to 11% in the placebo group. About 38% of participants in the durvalumab group developed pneumonia, a known side effect of these radiotherapy and immunotherapy treatments, compared to 30% in the placebo group.
Towards a new standard of care
“Standard treatment for patients with limited-stage small cell lung cancer (SCLC) has not changed significantly since the 1980s. In this trial, patients with this cancer who received immunotherapy after traditional chemotherapy and radiotherapy lived longer and were less likely to have their cancer return” underlines Professor Lauren Byers, from the department of medical oncology at the prestigious MD Anderson Cancer Center.
Researchers continue to follow study participants to assess whether there are better outcomes in patients who take a combination of durvalumab and tremelimumab (another immunotherapy with a different target: CTL-4) and to determine whether within this population if certain patients obtain better results to identify prognostic response criteria.