Encorafenib

Pfizer has shared positive survival results from a late-stage study of its Braftovi (encorafenib) regimen in patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC). Data from the phase 3 BREAKWATER trial, which has been evaluating the drug in combination with Eli Lilly/Merck KGaA’s Erbitux (cetuximab) and mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin), was presented at this year’s American Society of Clinical Oncology (ASCO) annual meeting. The Braftovi regimen was shown to reduce the risk of disease progression or death by 47% compared to standard-of-care chemotherapy with or without bevacizumab, meeting the study’s dual primary endpoint. Results from a second interim analysis of overall survival, a key secondary endpoint, also demonstrated that the Braftovi regimen lowered the risk of death by 51% compared to chemotherapy with or without bevacizumab. Around 154,270 people are expected to be diagnosed with cancer of the colon or rectum in the US this year. BRAF mutations are estimated to occur in up to 12% of those with metastatic cases of the disease and are associated with a poor prognosis. Taken orally, Braftovi is a small molecule kinase inhibitor designed to target the most common BRAF mutation, BRAF V600E, which more than doubles patients’ risk of death compared to those with no known mutation present. Braftovi, in combination with Erbitux and mFOLFOX6, was granted accelerated approval in the US at the end of last year to treat patients with BRAF V600E-mutant mCRC. The authorisation was based on a clinically meaningful and statistically significant improvement in confirmed objective response rate, BREAKWATER’s other dual primary endpoint. Pfizer outlined that the BREAKWATER survival data is now being discussed with the FDA to support the potential conversion to full approval for the combination in this indication. Johanna Bendell, chief oncology development officer at Pfizer, said: “The Braftovi combination helped significantly reduce the risk of disease progression or death, potentially altering the course of disease for people with mCRC with a BRAF V600E mutation. “These unprecedented results from the BREAKWATER trial further establish the benefit of the Braftovi combination regimen and its potential to become a new standard of care…” Pfizer has exclusive rights to Braftovi in the US, Canada, Latin America, the Middle East and Africa, while licences are also held by Ono Pharmaceutical, Medison and Pierre Fabre.

A slew of late-breaking presentations were shared at the American Society of Clinical Oncology this weekend, featuring potentially practice-changing results in colorectal, breast and gastric cancers. ATOMICRoche reported results from the Phase III ATOMIC study evaluating the addition of its PD-L1 inhibitor Tecentriq (atezolizumab) to standard FOLFOX chemotherapy in 712 patients with DNA mismatch repair (dMMR) colon cancer.After a median follow-up of 37.2 months, patients given the Tecentriq combo had a 50% lower risk of recurrence and death compared to patients treated with FOLFOX alone.The data could "change the standard of care" for dMMR colon cancer patients by embracing the addition of Tecentriq to FOLFOX in the adjuvant setting, said Joel Saltzman, vice chair of regional oncology at the Cleveland Clinic's Taussig Cancer Center.NIVOPOSTOPBristol Myers Squibb said its PD-1 inhibitor Opdivo (nivolumab) lowered the risk of cancer recurrence when added to chemoradiotherapy (CRT), based on the results of the Phase III NIVOPOSTOP study in 666 patients with resected locally advanced head and neck squamous cell carcinoma (HNSCC). Patients who received Opdivo plus CRT had a 24% boost to disease-free-survival versus CRT alone after 30.3 months of median follow-up. Additionally, of those taking the combination, 63.1% had no signs of cancer recurrence three years post-treatment, compared with 52.5% for the CRT alone arm.SERENA-6AstraZeneca revealed findings from the Phase III SERENA-6 study, in which patients with HR-positive/HER2-negative advanced breast cancer who switched to treatment with the oral selective oestrogen receptor degrader (SERD) camizestrant following the emergence of an ESR1 mutation during first-line therapy had a 56% reduction in the risk of disease progression or death.SERENA-6 is the first registrational trial to use a circulating tumour DNA (ctDNA)-guided approach to detect the emergence of endocrine resistance and ESR1 mutations in patients receiving first-line treatment with an aromatase inhibitor plus a CDK4/6 inhibitor. After mutation emergence, 157 patients continued with a CDK4/6 but were switched off the aromatase inhibitor and on to camizestrant, while 158 participants continued treatment with both an aromatase inhibitor and CDK4/6 inhibitor.Results showed that the camizestrant arm achieved progression-free survival (PFS) of 16 months, versus 9.2 months in the control group. At one-year, the PFS rate was 60.7% in the camizestrant group, compared to 33.4% for controls, while the rates at two years were 29.7% and 5.4%, respectively.MATTERHORNAstraZeneca's Imfinzi (durvalumab) became the first immunotherapy to demonstrate a statistically significant and clinically meaningful improvement in event-free survival (EFS) when used in the perioperative treatment setting for patients with early-stage gastric cancer and gastroesophageal junction cancer.Results from the Phase III MATTERHORN study showed that the addition of Imfinzi to standard FLOT chemotherapy before and after surgery, with follow-up treatment with AstraZeneca's PD-L1 inhibitor alone, led to a 29% improvement in EFS, as well as "a strong trend" in overall survival, compared to the FLOT regimen.Lead author Yelena Janjigian suggested that the findings "will change practice," noting that "the use of immunotherapy in earlier-stage cancers, as demonstrated in this perioperative approach…can reduce the risk of recurrence and improve cure rates."VERIFYTakeda and Protagonist presented detailed findings from the Phase III VERIFY study of rusfertide in polycythemia vera (PV), highlighting further benefits of the hepcidin mimetic beyond previously shared top-line results. New data showed significantly fewer rusfertide-treated patients required phlebotomy versus placebo recipients (27% vs 78%), and 62.6% of participants in the rusfertide group maintained haematocrit levels below 45% versus 14.4% in the placebo group. Safety outcomes were also shared for the first time in detail. No serious adverse events were linked to treatment, and the frequency of cancer events was significantly lower in the rusfertide group (0.7%) compared with placebo (4.8%).BREAKWATERPfizer said incorporating its kinase inhibitor Braftovi (encorafenib) into a combination therapy can cut the risk of death in half, based on results from the Phase III BREAKWATER study in patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC).  Patients given Braftovi in combination with the EGFR inhibitor Erbitux (cetuximab) and chemotherapy had a 51% lower risk of dying and a 47% lower risk of progression than those treated with chemotherapy with or without Avastin (bevacizumab). Additionally, those taking the triplet achieved overall survival (OS) of 30.3 months and PFS of 12.8 months, versus 15.1 months and 7.1 months, respectively, for those in the control arm.ASCENT-04/KEYNOTE-D19Gilead Sciences reported that combining its Trop-2-directed antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan-hziy) with Merck & Co.'s PD-1 inhibitor Keytruda (pembrolizumab) improved survival in the 443-patient Phase III ASCENT-04/KEYNOTE-D19 study evaluating the duo in previously untreated, PD-L1-positive (CPS ≥10) metastatic triple-negative breast cancer (TNBC).Trodelvy plus Keytruda cut the risk of disease progression or death by 35% compared with the current standard of Keytruda plus chemotherapy, extending median PFS to 11.2 months versus 7.8 months for the control arm.Editors Anna Bratulic, Matthew Dennis, Elizabeth Eaton and Pavan Kamat contributed to this report.