Landscape of Combination Immunotherapy and Targeted Therapy to Improve Cancer Management

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

person-from-dots-2307944_960_720

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.

Full reference: Colli, L.M. et al. (2017) Landscape of Combination Immunotherapy and Targeted Therapy to Improve Cancer Management. Cancer Research. Vol. 77(no. 13) pp. 3666–71

Immunotherapy improves the prognosis of lung cancer: do we have to change intensive care unit admission and triage guidelines?

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 [1]. 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.

Read the full article here

Localized immunotherapy new possibility to treat bladder cancer

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.

Read the full overview here

Read the original research abstract here

Immunotherapy for breast cancer: past, present, and future

Spellman, A. & Tang, S.C. Cancer Metastasis Review. Published online:02 December 2016

medic-563423_960_720.jpg

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.

Read the full abstract here

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck

Ferris, R.L. New England Journal of Medicine. Published online: 9 October 2016

N0009269 Cancer of the tongue

Image source: Wellcome Images // CC BY-NC-ND 4.0

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.

Read the full article here

Cancer tumour genetics reveal possible treatment revolution

Ian Sample. The Guardian Healthcare. Published online: 4th March 2016.

A landmark discovery into the genetic makeup of tumours has the potential to open a new front in the war on cancer, delivering potent therapies that are tailored to individual patients, scientists have said.

The breakthrough comes from research into the genetic complexity of lung and skin cancers which found that even as tumours grow and spread around the body, they carry with them a number of biological “flags” that the immune system can be primed to attack.

Because the flags, which appear as surface proteins, are found only on cancer cells, they provide what scientists described as “exquisite targets” for new therapies that draw on the power of the immune system to combat cancer.

Treatments that harness the immune system have shown great promise against some forms of cancer, such as melanoma, but they do not work in everyone. One approach releases the brakes on the immune system, unleashing the full force of killer T cells, which are otherwise dampened down by cancer cells. But to work, the patient’s immune system must first recognise the cancer as the enemy.

Read the full news article here