Week's news analysis
What was up at virtual ESMO 2021
ESMO 2021 /DR
The world of cancer research, diagnostics and therapeutics led its virtual congress on the European Society of Medical Oncology (ESMO) website for the second year in row due to the Covid-19 pandemic. Here are some of the main highlights of the biggest congress in Europe, as if you were attending the meetings
- Breast cancer at ESMO 2021
Still in the field of breast cancer, Novartis announced that the final overall survival (OS) analysis of the Phase III MONALEESA-2 trial demonstrated that endocrine therapy with CDK4/6 inhibitor Kisqali (ribociclib) prolonged OS by over 12 months compared to placebo in postmenopausal women with HR+/HER2- advanced breast cancer in the first-line setting. According to the swiss company, this result makes Kisqali the only CDK4/6 inhibitor with proven OS benefit across all three Phase III trials of the MONALEESA programme with different endocrine therapy partners, regardless of menopausal status or line of therapy. OS was evaluated after 400 deaths and showed a median duration of 63.9 months for Kisqali-treated patients, compared with 51.4 months for placebo, translating to a 24% reduction in the risk of death.
Merck & Co. unveiled updated study results demonstrating that adding its checkpoint inhibitor Keytruda (pembrolizumab) to chemotherapy in the first-line setting reduced the risk of death by 27%, compared to chemotherapy alone, in patients with metastatic triple-negative breast cancer (TNBC) whose tumours express PD-L1 with a combined positive score (CPS) ?10. Detailed findings from the Phase III KEYNOTE-355 trial (847 patients with locally recurrent inoperable or metastatic TNBC that has not been previously treated with chemotherapy in the advanced setting) revealed OS benefit of nearly seven months. Median OS for the higher PD-L1 expressers was 23 months, versus 16.1 months for placebo. Lower-expressing PD-L1 patients achieved median OS of 17.6 months and PFS 7.6 months.
- Lung Cancer at ESMO 2021 BeyondSpring Pharmaceuticals released detailed results from the Phase III DUBLIN-3 study, with the combination of plinabulin and docetaxel showing a significant improvement in overall survival (OS) versus docetaxel alone for the treatment of second- or third-line non-small-cell lung cancer (NSCLC) patients with EGFR wild type. Results showed that OS was 15.1 months for plinabulin plus docetaxel, compared to 12.8 months for docetaxel alone, while median OS in the two treatment groups was 10.5 months and 9.4 months, respectively. The study also met key secondary endpoints, with plinabulin plus docetaxel showing significant improvements versus docetaxel alone on overall response rate and progression-free survival (PFS), as well as 24- and 36-month OS rates.
- Head and neck cancers at ESMO 2021 Bristol Myers Squibb released the first detailed results from the Phase III CheckMate -651 trial showing that median overall survival (OS) for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) who received the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) was 13.9 months versus 13.5 months for the EXTREME regimen of cetuximab, cisplatin/carboplatin and fluorouracil. Furthermore, updated results were also released from the Phase III CheckMate -649 trial, which enrolled adults with previously untreated, unresectable advanced or metastatic gastric cancer, gastroesophageal junction cancer or oesophageal adenocarcinoma, regardless of their PD-L1 expression levels. The benefits of Opdivo plus chemotherapy remained with a further one year of follow-up, with a 30% reduction in the risk of death and a 12% improvement in the 24-month OS rate.
- Colorectal cancer at ESMO 2021 Amgen revealed data from a Phase Ib/II study (CodeBreakK 101) showing that combining Lumakras (sotorasib) with the EGFR inhibitor Vectibix (panitumumab) in patients with KRAS G12C-mutated advanced colorectal cancer led to "encouraging response rates that were much higher than the 9.7% response rate observed with Lumakras monotherapy". The study showed that among 26 patients in the efficacy analysis set, the objective response rate (ORR) was 27%, with seven confirmed and unconfirmed partial responses, while the disease control rate (DCR) was 81%. Furthermore, in 18 patients who had not received Lumakras before, the ORR was 33%, with six confirmed and unconfirmed partial responses, while the DCR was 83%. Based on these results, the group announced the initiation of a new Phase III trial with Lumakras plus Vectibix in the third-line setting. Separately on Thursday, Amgen detailed a collaboration to evaluate Lumakras with Boehringer Ingelheim's experimental SOS1::pan-KRAS inhibitor BI 1701963, specifically for people living with lung and colorectal cancers.
- Gastric cancers at SMO 2021 Leap Therapeutics announced that a Phase IIa study of its DKK1 antibody DKN-01, in combination with BeiGene's anti-PD-1 antibody tislelizumab, produced "compelling activity" in first-line patients with gastric or gastroesophageal junction cancer (G/GEJ). In the primary efficacy analysis, including all patients who received a full cycle of DKN-01 therapy, the objective response rate (ORR) was 68.2%, with 90% ORR in DKK1-high patients and 56% ORR in DKK1-low patients. In the overall intent-to-treat population, which included those who did not receive a full cycle of therapy, the ORR was 60%. When broken down into DKK1-high and DKK1-low patients, the ORRs were 75% and 56%, respectively. Median duration of response and progression-free survival were not reached. Researchers noted that the mean duration of treatment was three months, with the longest to date being seven months, while 19 patients remain on therapy. Leap entered into a strategic partnership with BeiGene in 2020, granting the latter rights to develop DKN-01 in Asia, Australia and New Zealand, excluding Japan.
Zymeworks revealed that its HER2 targeted bispecific antibody zanidatamab showed "promising response rates and durability" when paired with chemotherapy in a Phase II trial of first-line patients with gastroesophageal adenocarcinoma (GEA). "Herceptin (trastuzumab) and chemotherapy have been the standard of care in first-line HER2-positive GEA for over 10 years," explained the company, adding it had developed a next-generation HER2-targeted agent. The ongoing study, dubbed ZWI-ZW25-201, is evaluating zanidatamab plus standard first-line chemotherapy regimens in subjects with locally advanced, unresectable or metastatic HER2-expressing gastrointestinal cancers, including GEA. Results after a median follow-up of 6.9 months showed zanidatamab plus chemotherapy had a confirmed objective response rate (ORR) of 75% and disease control rate (DCR) of 89% overall. Based on the results, Zymeworks plans to start enrolling first-line GEA patients in the Phase III HERIZON-GEA-01 in the fourth quarter to test zanidatamab plus CAPOX or FP, with or without BeiGene's PD-1 inhibitor tislelizumab, versus standard care with Herceptin plus chemotherapy.
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