Imfimzi (durvalumab) has demonstrated a significant benefit in overall survival and in lasting response rates in small cell lung cancer with extended disease in previously untreated patients.
This is indicated by the results of the Phase III CASPIAN trial presented by AstraZeneca at the Presidential Session of the IASCL World Lung Cancer Congress 2019 organized by the International Association for the Study of Lung Cancer held in Barcelona.
They indicate that durvalumab, in combination with four cycles of standard chemotherapy treatment (etoposide in combination with cisplatin or carboplatin), demonstrated a statistically significant and clinically relevant improvement in overall survival (OS) compared to the standard treatment consisting of up to six cycles of chemotherapy and optional prophylactic cranial radiotherapy.
Regarding the risk of death, it was reduced by 27 percent (equal to a hazard ratio of 0.73) with a median OS of 13.0 months for durvalumab in combination with chemotherapy compared to 10.3 months for standard treatment . On the other hand, a prolonged benefit in OS was found with an estimated 33.9 percent of patients who remained alive at 18 months after treatment with durvalumab in combination chemotherapy compared to 24.7 percent of patients who They received the standard treatment.
Benefits were observed in all efficacy objectives in patients treated with durvalumab in combination chemotherapy versus standard treatment. The results showed a progression-free survival rate (PFS) greater than 12 months (17.5 percent versus 4.7 percent), a 10.3 percent increase in the objective response rate (ORT). confirmed (67.9 percent versus 57.6 percent), and a better response duration (DR) rate at 12 months (22.7 percent versus 6.3 percent).
In view of the results, José Baselga, executive vice president of R&D in Oncology, said: “We are encouraged to see that more than one third of patients with microcytic lung cancer treated with durvalumab in combination with chemotherapy are still alive at 18 months, which is noteworthy, given the aggressive nature of the disease. It is also noteworthy that these results allow healthcare professionals to choose durvalumab in combination with chemotherapy treatment based on both cisplatin and carboplatin. We look forward to working with regulatory authorities to bring durvalumab to patients with small cell lung cancer worldwide as soon as possible. ”
For his part, Luis Paz-Ares, Head of Service of the University Hospital Doce de Octubre in Madrid, and principal investigator of the Phase III CASPIAN trial, explains that “patients have had limited treatment options for microcytic lung cancer, a disease devastating with a low five-year survival rate of only 6 percent. The significant survival benefit demonstrated by durvalumab in combination with only four cycles of chemotherapy at the investigator's choice compared to a solid control arm, provides evidence and hope for a new treatment option for these patients, ”says the expert.
The safety and tolerability of durvalumab in combination with standard treatment with etoposide and platinum-based chemotherapy was consistent with previous clinical trials. The results showed that 61.5 percent of patients experienced Grade 3 or 4 adverse events (AA) with durvalumab plus standard treatment (for any cause) versus 62.4 percent with standard treatment, and Patients who discontinued treatment due to AA were similar between both arms (9.4 percent versus 9.4 percent).
Durvalumab is also being investigated in CPM in limited disease after concurrent chemoradiotherapy in the Phase III ADRIATIC trial.
Durvalumab is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, counteracting the escape routes of the tumor to the immune response and canceling the inhibition of the immune response.
It is approved for unresectable stage III non-small cell lung cancer in 49 countries, such as the USA. USA, the EU and Japan, based on the Phase III PACIFIC trial.
In Europe, durvalumab monotherapy is indicated in adults for the treatment of locally advanced, non-resectable non-small cell lung cancer (NSCLC), whose tumors express PD-L1 ≥ 1 percent in tumor cells and whose disease has not progressed afterwards. of platinum-based chemoradiotherapy.
Currently, in Spain it is in the process of obtaining price and reimbursement by the health authorities. Durvalumab monotherapy is indicated in adults for the treatment of locally advanced, non-resectable non-small cell lung cancer (NSCLC), whose tumors express PD-L1 ≥ 1 percent in tumor cells and whose disease has not presented progression after chemoradiotherapy based in platinum
The CASPIAN trial is a randomized, open, multicenter, global Phase III trial that evaluates the first-line treatment of patients with CPM with extended disease. The trial compares durvalumab in combination with chemotherapy with cisplatin or carboplatin and etoposide, or the combination of durvalumab, Tremelimumab and chemotherapy versus chemotherapy alone. In the experimental groups, patients were treated with up to four cycles of chemotherapy. In comparison, the control group allowed up to six cycles of chemotherapy and optional PCI. The trial will continue until the final SG analysis for the combination of durvalumab, tremelimumab and chemotherapy.
The trial is being carried out in more than 200 centers in 22 countries, such as the United States, Europe, South America, Asia and the Middle East. The primary objective is the GS.