Immunotherapy for lung cancer! Mosadon keytruda combined with first-line chemotherapy significantly prolonged progression free survival, not related to KRAS mutation!

December 17, 2019 / BIOON / -- cancer immunotherapy giant Merck & Co recently released exploratory analysis data of key phase III keynote-189 (nct02578680) study of lung cancer The results showed that in NSCLC patients, anti-PD-1 therapy (coreda, common name: pembrolizumab, pabolizumab) combined with Alimta (pemetrexed) and platinum chemotherapy for first-line treatment improved PFS and orr, regardless of KRAS mutation The keynote-189 study was conducted by mosadon and Lilly, a randomized, double-blind, placebo-controlled study 616 patients with metastatic nsnsclc who had not been treated before (primary treatment) were enrolled These patients did not consider their PD-L1 tumor expression status, and did not have EGFR or ALK genomic tumor distortion, nor did they receive systematic therapy for advanced diseases In the study, patients were randomly assigned to two treatment groups: (1) keytruda treatment group (n = 410), received keytruda (200mg) + platinum (cisplatin or carboplatin) + pemetrexed (500mg / m2, q3w) chemotherapy for four cycles, and then received keytruda (200mg) and pemetrexed (500mg / m2, q3w); (2) placebo group (n = 206), received platinum (cisplatin or carboplatin) + pemetrexed (500) Mg / m2, q3w) chemotherapy for 4 cycles, followed by pemetrexed (500mg / m2, q3w) In the study, patients were treated until their condition progressed or their toxicity was unacceptable The main outcome measures were total survival (OS) and progression free survival (PFS) assessed by BICR according to RECIST v1.1 The secondary outcome measures were overall response rate (ORR) and duration of response (DOR) In the study, patients in the chemotherapy group were allowed to turn to open label keytruda treatment if their progress was confirmed by independent review of the center Previously published data showed that the study reached the common primary end point of OS and PFS: compared with chemotherapy alone, keytruda treatment group achieved statistically significant and clinically significant improvement in OS (median OS: less than vs 11.3 months, HR = 0.49 [95% CI: 0.38-0.64], P < 0.0001), PFS also achieved significant improvement (median PFS: 8.8 months vs 4.9 months, HR = 0.52 [95% CI: 0.43-0.64], P < 0.0001) In terms of secondary end points, Orr was significantly increased (48% vs 19%, P < 0.0001) and Dor was prolonged (11.2 months vs 7.8 months) in keytruda group The purpose of this exploratory analysis was to evaluate the mutation rate of KRAS mutation in the keynote-189 study and its relationship with efficacy Whole exome sequencing (WES) was used to assess KRAS status and tumor mutation burden (TMB) Among the 616 primary NSCLC patients, 289 (47%) had Wes data from tumor and normal DNA simultaneously Of these 289 patients, 89 (31%) had mutations in KRAS, including 37 (13%) with mutations in KRAS G12C The results showed that keytruda + chemotherapy was associated with improved clinical prognosis in patients with metastatic non squamous NSCLC, regardless of KRAS mutation status, compared with placebo + chemotherapy In this analysis, keytruda + chemotherapy reduced the risk of disease progression or death in patients with any KRAS mutation, KRAS G12C mutation and no KRAS mutation by 53%, 52% and 60%, respectively, compared with placebo + chemotherapy The safety of keytruda is consistent with the previously reported results in patients with metastatic NSCLC KRAS mutations occur in about 20% of NSCLC patients, and some previous studies have shown that these mutations are related to poor response to treatment Therefore, in this exploratory analysis, keytruda + chemotherapy regimens were associated with survival benefits in patients with metastatic non squamous NSCLC, regardless of KRAS mutation status The results suggest that keytruda + chemotherapy should be the standard first-line regimen for patients with metastatic NSCLC Other therapeutic results of this exploratory analysis show that lung cancer is the main cause of cancer death worldwide It is formed in lung tissue, usually in cells in the airway The two main types of lung cancer are non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) NSCLC is the most common type of lung cancer, accounting for about 85% of all cases NSCLC has many subtypes, including adenocarcinoma (40% of lung cancer), squamous cell carcinoma (25% - 30%) and large cell carcinoma (10% - 15%) Lung cancer can also be characterized by different biomarkers, including PD-L1, KRAS, ALK, EGFR and ros1 KRAS mutations occur in about 20% of NSCLC cases Keytruda belongs to PD - (L) 1 tumor immunotherapy, which helps detect and fight against tumor cells by improving the ability of human immune system Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2, thus activating T lymphocytes that may affect tumor cells and healthy cells So far, a number of PD - (L) 1 tumor immunotherapies have been approved worldwide, among which keytruda is the leader in this field and has approved more than 20 treatment indications MSD has the largest clinical development project in immunooncology in the industry At present, more than 1000 clinical trials are investigating the role of keytruda in various types of tumors and treatment backgrounds The keytruda clinical project aims to understand the role of the drug in cancer and factors that may predict patients' benefits from keytruda treatment, including exploring several different biomarkers At the end of November this year, keytruda was approved by China National Drug Administration (nmpa) to combine carboplatin and paclitaxel for the first-line treatment of metastatic squamous cell non-small cell lung cancer (NSCLC) It is worth mentioning that this approval is also keytruda's third first-line approval in NSCLC treatment in less than a year Now, the drug is the first anti PD-1 therapy approved by China for the first-line treatment of squamous and non squamous NSCLC combined with chemotherapy, and single drug treatment of NSCLC (tumor proportion score [TPS] ≥ 1%) Original source: KRAS national status and efficient in keynote-189: pembrolizumab (pembro) plus chemo therapy (chemo) vs placebo plus chemo as first line therapy for metric nonstamous NSCLC