Research progression on the first-line biological target therapy of advanced / 中国肿瘤生物治疗杂志

@#With the progress of gene detection technology and the speed-up in new drug development, biological target therapy has fully covered the first-line treatment of advanced NSCLC. Immunotherapy has significantly improved the survival of advanced NSCLC patients with negative driven genes, and the median OS reaches about 2 years (15.6-30 months). EGFR is the most common driven gene. According to different EGFR mutation subtypes (L858R or 19del), different treatment mode (EGFR-TKI single drug, TKI combined with anti-vascular drugs and TKI combined with chemotherapy) is selected as the first-line treatment, which has become a consensus. Depending on the data of median PFS, the treatment efficacy against rare targets is more prominent, which has exceeded the efficacy of standard chemotherap:ALK (alectinib, PFS=34.8 months), ROS1 (ceritinib, PFS=19.3 months), RET (selpercatinib, PFS=18.4 months), BRAF (dabrafenib plus trametinib, PFS=14.6 months), NTRK (larotrectinib, PFS≥12 months) and MET (savolitinib, PFS=9.7 months). In conclusion, the first-line treatment of advanced NSCLC has entered the era of“precision-targeted treatment”based on different molecular typing, and it has become a consensus that high-throughput sequencing is required for newly diagnosed patients.

Advances and optimization in the treatment schedule of HER2-positive breast cancer / 中国肿瘤生物治疗杂志

@# The efficacy and prognosis of human epidermal growth factor receptor 2 (HER2) positive breast cancer patients have been significantly improved with the development and wide application of anti-tumor drugs against HER2. The results of PEONY research once again established the status of the double-target treatment mode of pertuzumab+trastuzumab in the field of neoadjuvant therapy. Based on the two studies of TRYPHAENA and TRAIN-2, paclitaxel plus platinum should be the first choice chemotherapy scheme for anti HER2 double-target therapy, and the treatment course of 6 cycles is preferred. According to the consensus of neoadjuvant therapy experts in China and the latest follow-up results of adjuvant APT study, the neoadjuvant therapy is more suitable for patients with a tumor diameter of more than 3 cm and/or positive lymph nodes metastasis; T-DM1 should be the first choice of adjuvant therapy in patients, who didn’t obtain pCR after neoadjuvant treatment, and whether the double-target adjuvant mode of pertuzumab plus trastuzumab is suitable depends on follow-up of the PEONY study. Low-risk patients with small tumors (<3 cm) and without lymph node metastasis may consider omitting neoadjuvant therapy but adopt direct surgery followed by postoperative adjuvant therapy with trastuzumab plus paclitaxel. The regimen of trastuzumab+pertuzumab combined with taxanes is still the standard first line treatment of late stage HER2+ patients; for Chinese patients, pyrotinib combined with capecitabine can be used as the second line optimization, and T-DM1 can be used as the third line and posterior line selection; when trastuzumab, pertuzumab and T-DM1 fail the treatment, DS-8201 becomes a new selection mode. Combined treatment mode of tucatinib plus trastuzumab and capecitabine can be considered in late stage HER2+ patients with brain metastases.

Advances in the clinical management of HER2-positive breast cancer / 中国肿瘤生物治疗杂志

@#人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）阳性乳腺癌侵袭性高，预后差。随着抗HER2 药物的不断出现及广泛应用，HER2阳性乳腺癌患者的预后出现了非常显著的改善。10年随访结果证实1年曲妥珠单抗辅助治 疗可以显著降低疾病复发风险；对于术后的高危人群，曲妥珠单抗联合帕妥珠单抗或者曲妥珠单抗序贯来那替尼可以进一步减 少复发。5年随访结果表明帕妥珠单抗+曲妥珠单抗为基础的新辅助治疗可使病理完全缓解（pathological complete response， pCR）转化为长期生存获益；白蛋白紫杉醇代替普通紫杉醇与抗HER2药物联用可以进一步提高pCR率；而抗HER2药物联合内 分泌治疗尚不能达到与联合化疗在新辅助治疗中疗效，即使联合CDK4/6抑制剂，对于pCR的提高依然有限。曲妥珠单抗+帕妥 珠单抗联合紫杉类药物是晚期HER2阳性乳腺癌的标准一线方案；对于老年、体弱的患者，节拍环磷酰胺可以作为紫杉类药物的 替代品；拉帕替尼+曲妥珠单抗联合内分泌治疗可以作为HER2阳性伴激素受体阳性的选择，疗效优于曲妥珠单抗联合内分泌治 疗；T-DM1无论是作为二线治疗还是三线及以后的治疗均提高了患者生存获益，是治疗晚期、耐药HER2阳性乳腺癌的首选。