We recently returned from the European Society for Medical Oncology (ESMO) 2017 meeting, which is the major meeting for oncology professionals in Europe, attracting over 24,000 participants from 131 countries. This fall meeting saw a lot of news, notably in the areas of lung cancer, breast cancer, and melanoma as well as immuno-oncology generally, including the area of liquid biopsy and biomarkers. Also of hot interest were a number of topics relating to access to new drugs in the European Union.
As result, we’d like to discuss a few highlights, first in the treatment setting:
AstraZeneca reported strong clinical results from trials of both Imfinzi and Tagrisso (osimertinib) in non-small cell lung cancer. In the PACIFIC lung cancer maintenance trial, they reported that Imfinzi cut the risk of disease progression by 48% in patients with Stage 3 NSCLC that was not resolvable by surgery but which had not yet progressed following standard platinum-based chemotherapy concurrent with radiation therapy. Investigators reported a median progression-free survival of 16.8 months for Imfinzi versus 5.6 months for placebo; overall survival data was not yet available. Stage 3 NSCLC accounts for about one-third of all NSCLC patients, and AstraZeneca recently received a breakthrough designation from FDA for Imfinzi in patients with locally advanced unresectable lung cancer.
AstraZeneca also reported exciting results from its FLAURA Phase 3 study of Tagrisso (osimertinib) as a potential first-line treatment for NSCLC patients with a specific EGFR mutation. Investigators presenting data showing that Tagrisso extended progression-free survival to a median of 18.9 months versus 10.2 months for either of the standard therapies, Tarceva (erlotinib) or Iressa (gefitinib). Moreover, Tagrisso-treated patients experienced lower rates of adverse events than those older treatments, and the treatment benefits were consistent even in patients with brain or central nervous system metastases. AstraZeneca reportedly plans to file for approval of Tagrisso in this indication in the near future.
Merck also reported good data for Keytruda (pembrolizumab) in combination with chemotherapy in first-line NSCLC. Updated data from their Phase 2 KEYNOTE-021 study showed a median progression-free survival for the combination of 19 months versus 8.9 months for chemotherapy alone, and an overall 18-month survival rate of 70% versus 56% for chemotherapy alone.
There was good news for hormone receptor-positive breast cancer patients as Eli Lilly reported positive results from its MONARCH 3 trial of abemaciclib in postmenopausal women with HR-positive, HER2-negative breast cancer — backing up the earlier positive data from MONARCH 1 and MONARCH 2 that supported a priority review designation from FDA. Adding abemaciclib to endocrine therapy with an aromatase inhibitor cut the risk of disease progression or death by 46%. Overall response rate in the abemaciclib-treated patients was 59.2% versus 44% in patients who received placebo.
Results of a study to explore the value of immune induction with chemotherapy or radiation, prior to treatment with a checkpoint inhibitor saw promising early results for Bristol-Myers Squibb’s Opdivo (nivolumab). In the ongoing Phase 2 TONIC trial, 50 patients with metastatic triple-negative breast cancer (TNBC) receive either two weeks of low-dose chemotherapy (3 different regimens) or radiation, before receiving treatment with Opdivo until disease progression. For the 50 evaluable patients reported at ESMO, the objective responsive rate was 24%; previously reported trials of single-agent anti-PD-1/PD-L1 immunotherapy in unselected patients with TNBC demonstrated response rates of approximately 5-10%. Overall survival at Year 1 exceeded 80% in those patients who had either a complete or partial response to the sequential treatments. The aim of the induction therapy was to prime the immune system before giving Opdivo, turning “cold” non-immunogenic tumors into “hot” immunogenic ones, attracting more immune cells to the tumor microenvironment before stimulating them with the checkpoint inhibitor. In a further win for patients, the safety data for the trial were in line with other immunotherapy studies, suggesting that such induction did not add to overall toxicity.
BMS reported a significant advance in adjuvant therapy for patients with surgically resected Stage III/IV melanoma with a high risk of relapse. In the CHECKMATE 238 study, which had been stopped early due to benefit, adjuvant therapy with Opdivo increased relapse-free survival in melanoma patients by 35% compared to adjuvant Yervoy (ipilimumab), the current standard of care. Grade 3 or higher adverse events were also reduced by about a third in adjuvant Opdivo-treated patients versus those receiving adjuvant-Yervoy therapy.
In Stage III melanoma patients with high risk mutations including BRAF, an indication where no standard-of-care adjuvant therapy yet exists, the combination of Tafinlar (dabrafenib, which blocks BRAF) and Mekinst (trametinib, a MEK inhibitor) following surgery produced a significant benefit over placebo for both overall patient survival and the risk of distant metastases. Results of the Phase 3 COMBI-AD study, sponsored by Novartis, saw a 53% lower risk of relapse or death compared to placebo. At a median follow up of 2.8 years, the 3 year rate of relapse-free survival was 58% for those receiving the drug combination versus 39% for placebo. There was also a benefit on overall survival: at 3 years, 86% of patients treated with the combination were still alive compared to 77% of placebo-treated patients, and the risk of distant metastases was lower by 49%. The combination therapy was associated with adverse events; 97% of those treated did experience some adverse event and 49% of those were serious AEs, versus 88% and 14% for placebo.
In our next post, we’ll talk about ESMO news in the biomarker and liquid biopsy area.