Keep checking back throughout the conference, we will be updating this article with the biggest news headlines from the American Association for Cancer Research (AACR) Annual Meeting 2018 (April 14–18, IL, USA). Highlights include:
KEYTRUDA scores big again in NSCLC Phase III KEYNOTE-189 study
Details of the KEYNOTE-189 study have been announced by Merck (known as MSD outside the United States and Canada).
The results demonstrate that its anti-PD-1 therapy, pembrolizumab, significantly improves overall survival (OS) in combination with pemetrexed (ALIMTA®) and cisplatin or carboplatin for the first-line treatment of metastatic nonsquamous non-small cell lung cancer (NSCLC), reducing the risk of death by half compared with chemotherapy alone.
“The results of this trial have the potential to change the treatment paradigm for patients with nonsquamous NSCLC in the first-line setting, including patients whose tumors are either PD-L1 negative or are untested,” explained Roger Perlmutter, Merck Research Laboratories (NJ, USA).
Pembrolizumab is the first immunotherapy to significantly extend survival of patients with nonsquamous NSCLC in combination with chemotherapy as a first-line treatment.
Nivolumab, ipilimumab combo triples progression-free survival in NSCLC patients with high TMB
Initial results from the Phase III CheckMate-227 study have been announced. The pivotal study has demonstrated that the combination of Opdivo® (nivolumab) plus Yervoy® (ipilimumab) can significantly extend progression-free survival (PFS) in those with previously untreated advanced NSCLC whose tumors have high tumor mutation burden (TMB).
The PFS rate in patients with high TMB was more than three times higher, when treated with the combination of nivolumab and ipilimumab compared to chemotherapy, with 1-year PFS rates of 43% and 13%, respectively.
In addition, the overall response rate (ORR), was greater with the combination (45.3%), versus chemotherapy (26.9%). At 1 year, 68% of responders in the combination arm had ongoing responses, compared to 25% for those treated with chemotherapy.
Source: Hellmann MD, Ciuleanu TE, Pluzanski A et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden New Eng. J. Med. doi:10.1056/NEJMoa1801946 (2018) (Epub ahead of print); www.businesswire.com/news/home/20180416005761/en/Opdivo-Low-Dose-Yervoy-Combination-Reduces-Risk-Progression
Positive data announced for pembrolizumab in adjuvant melanoma
Positive late-stage data has been announced from the KEYNOTE-054 trial, investigating pembrolizumab in high-risk stage III melanoma patients.
In this trial, pembrolizumab significantly prolonged recurrence-free survival (RFS), reducing the risk of disease recurrence by 43% compared with placebo as an adjuvant therapy in resected, high-risk stage III melanoma patients.
Pembrolizumab is the first anti-PD-1 therapy to demonstrate RFS benefit across stage IIIA (> 1 mm lymph node metastasis), IIIB and IIIC melanoma. The RFS benefit was also seen regardless of BRAF mutation status.
Pembrolizumab and chemotherapy combo doubles survival in metastatic lung cancer
According to an international Phase III trial, pembrolizumab combined with chemotherapy doubles survival in patients with non-squamous non-small cell lung cancer (NSNSCLC) lacking genetic changes in the EGFR or ALK genes, when compared to chemotherapy alone.
A total of 616 patients with untreated, metastatic NSNSCLC without EGFR or ALK alterations, from 118 international sites, were randomly allocated for the trial. Of these, 405 patients were treated with both pembrolizumab and platinum plus pemetrexed, and 202 received platinum plus pemetrexed with a saline placebo.
Response rates, OS and PFS rates were superior in the pembrolizumab and chemotherapy combination-treatment group.
Of those treated with pembrolizumab and platinum plus pemetrexed, the risk of death was reduced by 51%, compared with those treated with platinum plus pemetrexed alone. Among patients treated with the combination therapy, the chance of progression or death was reduced by 48%. In other words, chance of overall and progression free survival doubled.
Promising immunotherapy strategy discovered for stage I–III NSCLC patients
A compelling study from the Stand Up To Cancer-Cancer (SU2C) Research Institute Cancer Immunology Dream Team has discovered a novel approach for treating lung cancer, whereby immunotherapy is administered prior to surgery.
The multi-institutional group of researchers discovered that administering two doses of the anti-PD1 immunotherapy nivolumab for several weeks prior to surgery was not only safe but 45% of the patients in the trial responded so well that there was little evidence of the cancer remaining upon follow-up.
After a median follow-up of 12 months, three-quarters of the patients who underwent surgical resection were alive and recurrence-free. Recurrence-free survival at 18 months was 73%, and the median recurrence-free survival had not been reached at the time of data analysis. To date, only one patient has died of cancer recurrence after surgery. SU2C is cautious not to compare these outcomes with historical outcomes given that it was a small study.
Traditionally, chemotherapy or chemoradiotherapy, is administered to lung cancer patients to shrink a large, non-metastasized tumor and in the past, immunotherapeutic agents have been administered after surgery with limited results.
In this study SU2C researchers hypothesized that leaving the tumor in place during initial treatment with immunotherapy would turn it into an “auto-vaccine” resulting in the activation of tumor-specific T cells that would then circulate through the body and find distant sites of micrometastases, thereby preventing relapse post-surgery which can happen to at least one-half of lung cancer patients who undergo surgery.