The battle for the end of the field of SCLC lung cancer with the first-line treatment of K medicine has failed!

Author: Mumu Drug K is very successful in the development of indications for lung cancer, especially non-small cell lung cancer Up to now, drug K has covered all indications of lung cancer, and only small cell lung cancer remains in the first-line treatment Keynote-604 test can be said to be the final battle in the field of lung cancer Yesterday, mosadon announced the phase III clinical trial (keynote-604) of keytruda, a blockbuster PD-1 inhibitor, combined with chemotherapy, in the first-line treatment of extensive small cell lung cancer (es-sclc) Results: the study reached one of its dual primary endpoints, namely, significantly improved patients' progression free survival (PFS), but the total survival (OS) did not reach a statistically significant level As a result, the shares of MSD fell about 2% this morning Source: Ifind, Zhongkang Industrial Capital Research Center Keynote-604 is a randomized, double-blind, placebo-controlled phase III trial of keytruda combined chemotherapy (in this case, etoposide plus cisplatin or carboplatin) In this study, 453 patients were recruited Compared with the chemotherapy alone for newly diagnosed es-sclc, the double primary end points were OS and PFS, and the secondary end points were objective response rate (ORR), response duration (DOR), safety and quality of life According to the results of this study, keytruda combined with etoposide, cisplatin or carboplatin reduced the risk of disease progression or death by 25% (HR = 0.75, 95% CI, 0.61-0.91) compared with chemotherapy, reaching the main end point of PFS significantly improved in patients, while OS results did not reach the statistical significant level (HR = 0.80, 95% CI, 0.64-0.98) in improving the overall survival of patients "The results of the keynote-604 trial show that keytruda, in combination with chemotherapy, can improve the prognosis of patients with this highly aggressive malignancy newly diagnosed as extensive small cell lung cancer," said Dr Roy Baynes, chief medical officer of the mossadon research laboratory "We sincerely thank the patients and researchers who participated in this study." Lung cancer includes non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) SCLC is a kind of neuroendocrine tumor Its molecular variation, growth rate and metastasis rate are different from NSCLC In addition, although SCLC is very sensitive to chemotherapy, its recurrence rate is very high After recurrence, SCLC becomes a kind of tumor that is difficult to treat Last year, the U.S Food and Drug Administration (FDA) approved the use of Roche's PD-L1 McAb tecentriq in combination with chemicals in patients with extensive SCLC, making it the first cancer immunotherapy approved for use in this indication Roche called it the first potential new front-line choice in the treatment of SCLC in 20 years In addition, AstraZeneca's imfinzi first-line treatment of extensive SCLC has also been given priority review by the US FDA Source: vantage, Zhongkang Industrial Capital Research Center Keytruda's two competitors have achieved success in the first-line treatment of SCLC: tecentriq and imfinzi have reduced the risk of death by 27% and 30% and extended the total survival time by 2.0 and 2.7 months in the impulse-133 and Caspian trials of similar design and similar patients, respectively Keytruda, who has always been in the wind and water, lost here Keytruda reduced the risk of death by 20% in the keynote-604 test, but failed to meet the pre-set statistical criteria It makes people want to find out why Citing a retrospective analysis published in JAMA, there is evidence that PD-L1 inhibitors such as tecentriq and imfinzi are more effective than keytruda in tumors with low PD-L1 expression and less applicability (such as SCLC) This hypothesis seems to be confirmed by keytruda's failure in the first-line treatment of SCLC in phase III and the earlier failure of opdivo of Bristol Myers Squibb in checkmate-451 Of course, it is also believed that PD-1 inhibitors still perform better than PD-L1 in general Back to keytruda, although it has reached the end point of PFS, considering that tecentriq and imfinzi have reached statistically significant levels of PFS and OS in the first-line treatment trial of SCLC, keytruda is less likely to be approved for this indication only based on the positive results of PFS However, whether the first-line treatment of SCLC is approved or not will not affect its use in the third-line treatment of SCLC In addition, keytruda's next key trial is keynote-355, a first-line treatment study for triple negative breast cancer, which can be followed up In fact, clinical trial failure is very common In terms of PD-1 / PD-L1, at least 21 items failed in phase III clinical trials, involving lung cancer, liver cancer, gastric cancer, head and neck cancer, triple negative breast cancer, glioblastoma, ovarian cancer, etc After the failure, we must learn from it When making clinical strategy, we should fully consider the boundary value setting of biomarkers, layered design, the balance of component population, the possible impact of follow-up treatment, the setting of end-point indicators and statistical analysis plan, so as to improve the success rate of clinical trials Source: vantage, Zhongkang Industrial Capital Research Center