BBC News | October 2018 | Nobel prize for medicine goes to cancer therapy
Two immunologists, Prof Allison, of the University of Texas, and Prof Honjo, of Kyoto University, as the winners of this year’s Nobel Prize for Medicine. The pair will share the Nobel prize approximately $1.01 million or £775,000. The scientists have been awarded the prize in recognition of their discovery of how to fight cancer using the body’s immune system. Their award is significant as it is the first time in the prize’s history that the development of a cancer therapy has been recognised with a Nobel prize.
Accepting the prize, Tasuku Honjo told reporters: “I want to continue my research … so that this immune therapy will save more cancer patients than ever.”
Prof Allison said: “It’s a great, emotional privilege to meet cancer patients who’ve been successfully treated with immune checkpoint blockade. They are living proof of the power of basic science, of following our urge to learn and to understand how things work.”(Source:BBC News).
Cancer treatments composed of immune checkpoint inhibitors and oncogene-targeted drugs might improve cancer management, but there has been little investigation of their combined potential as yet | Cancer Research
To estimate the fraction of cancer cases that might benefit from such combination therapy, we conducted an exploratory study of cancer genomic datasets to determine the proportion with somatic mutation profiles amenable to either immunotherapy or targeted therapy.
We surveyed 13,349 genomic profiles from public databases for cases with specific mutations targeted by current agents or a burden of exome-wide nonsynonymous mutations (NsM) that exceed a proposed threshold for response to checkpoint inhibitors.
Overall, 8.9% of cases displayed profiles that could benefit from combination therapy, which corresponded to approximately 11.2% of U.S. annual incident cancer cases. Frequently targetable mutations were in PIK3CA, BRAF, NF1, NRAS, and PTEN. We also noted a high burden of NsM in cases with targetable mutations in SMO, DDR2, FGFR1, PTCH1, FGFR2, and MET.
Our results indicate that a significant proportion of solid tumor patients are eligible for immuno-targeted combination therapy, and they suggest prioritizing specific cancers for trials of certain targeted and checkpoint inhibitor drugs.
Guillon, A. et al. Critical Care. Published online: 27 January 2017
Bald heads may soon not be a sign that identifies a cancer patient receiving treatment. Indeed, therapies for cancer patients are improving dramatically leading to increased survival rates, and most are associated with a different toxicity profile. Recently, antibody-based therapy has transformed the therapeutic landscape and biology of non-small cell lung cancer (NSCLC) and other solid tumors. This may also reshuffle the playing cards for an intensive care unit (ICU) admission policy due to improved outcomes.
In November 2016, the results of the KEYNOTE-024 trial showed for the first time the superiority of immunotherapy over chemotherapy as first-line treatment for NSCLC . In this phase 3 trial, a humanized monoclonal antibody (mAb) against programmed death 1 (PD-1) was tested in patients who had previously untreated advanced NSCLC. The clinical trial was stopped by the safety monitoring committee on the basis of substantial clinical benefit of immunotherapy, and patients remaining in the chemotherapy group were switched to receive immunotherapy.
New findings from IGP show an alternative way to administer the therapy, which has the same effect on the tumour but less impact other parts of the body | ScienceDaily
Image shows photomicrograph (magnification X60) of botyroidal rhabdomyoscarcoma of the bladder
In the study immune activation was achieved by administering blocking antibodies close to the tumour. The results complement the researcher’s previous findings where they found that a direct immune stimulatory antibody had superior anti-tumour capacity when used locally at the tumour, as compared to after injection into the blood.
The hope is also that the immune cells, not the drug itself, can find potential metastases and eliminate them. To understand if and how this is happening, further research is required. The present results are based on studies in mice and to determine if drug administration to the tumour results in fewer adverse events in patients, as compared to injections into the blood stream, clinical studies are also needed.
Spellman, A. & Tang, S.C. Cancer Metastasis Review. Published online:02 December 2016
Immunotherapy has shown promise in many solid tumors including melanoma and non-small cell lung cancer with an evolving role in breast cancer. Immunotherapy encompasses a wide range of therapies including immune checkpoint inhibition, monoclonal antibodies, bispecific antibodies, vaccinations, antibody-drug conjugates, and identifying other emerging interventions targeting the tumor microenvironment.
This review will focus on the current role and future directions of many of these immunotherapies in breast cancer, as well as highlighting clinical trials that are investigating several of these active issues.
Ferris, R.L. New England Journal of Medicine. Published online: 9 October 2016
Image shows photomicrograph of squamous cell carcinoma of the tongue.
Background: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti–programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition.
Methods: In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life.
Results: The median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P=0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P=0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group.
Conclusions: Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy.