Improving survival with immunotherapy
2015 has seen great progress in the use of immunotherapy to treat cancer, as highlighted in the opening plenary session. Caroline Robert honored Jim Allison’s discovery that that CTLA-4 blockade activates the immune system against cancer, which led to the development of ipilimumab, the first immunotherapy drug to extend the lives of patients with melanoma.
‘immunogenic targeted therapy’ and ‘personalized immunotherapy’ should be considered in future clincial trials
Robert discussed the latest findings showing that nivolumab, alone or combined with ipilimumab, has a striking effect on survival in patients with metastatic melanoma. Because some cytotoxic and targeted therapies impact the immune system, Robert recommended that individualized targeted therapy and immunotherapy should not be considered as separate strategies.
“…‘immunogenic targeted therapy’ and ‘personalized immunotherapy’ should be considered in future clincial trials” – Caroline Robert
A number of new results presented here at ECC2015 have demonstrated the tremendous potential of immunotherapy to extend the lives of people with cancer. Padmanee Sharma described findings from the CheckMate 025 study, showing that patients with advanced renal cell carcinoma treated with nivolumab have better overall survival than those given everolimus.
The results of two phase II clinical trials suggest that another type of immunotherapy, the PD-L1 inhibitor atezolizumab, is showing promise for the treatment of lung cancer. The POPLAR trial showed that atezolizumab significantly improved overall survival in non-small cell lung cancer patients when compared with docetaxel, while the BIRCH study suggested that atezolizumab monotherapy has efficacy in NSCLC patients selected based on PD-L1 expression. In the IMvigor 210 trial, Jonathan Rosenberg and colleagues found that atezolizumab has clinical benefit in patients with metastatic urothelial carcinoma.
A number of other presentations outlined the potential of immunotherapy to treat breast cancer, colorectal cancer and brain tumors. Together, these findings underscore the tremendous potential of immunotherapy to change clinical practice in oncology.
New treatment options for prostate cancer
There have been great improvements in the management of prostate cancer in recent years, as discussed by Bertrand Tombal in an overview of new drugs on the horizon. The results of the STAMPEDE trial presented by Nick James revealed that adding docetaxel to standard treatment for hormone-naïve prostate cancer improves overall survival. A subsequent meta-analysis presented by Claire Vale considered all the evidence, and Vale concluded that incorporating docetaxel into treatment strategies should be the new standard of care for these patients.
“Incorporating docetaxel into treatment strategies [for hormone-naïve prostate cancer] should be the new standard of care for these patients” – Claire Vale
Incorporating docetaxel into treatment strategies [for hormone-naïve prostate cancer] should be the new standard of care for these patients
Commenting on these studies, Ronald de Wit highlighted that the findings from the STAMPEDE trial and other studies suggest that docetaxel and androgen receptor-targeted agents present new options for patients with prostate cancer. However, de Wit cautioned that the optimal sequence for these agents has yet to be determined, and emphasized the importance of determining which patients are most likely to benefit from certain treatment strategies.
Anders Bjartell discussed the ways in which we can distinguish significant from non-significant cancers through predictive markers and studies on life expectancy, but emphasized that more work investigating patient-reported outcomes and tumor heterogeneity is required to better understand which prostate cancers are likely to require aggressive treatment.
Cancer genomics and precision medicine
Genomic analysis is increasingly being used in oncology to inform therapeutic decisions and predict prognosis. Carlos Caldas explained that breast cancer can be separated into 10 different diseases based on copy number and gene expression data, and discussed ongoing work to generate patient-derived xenograft models representing human breast cancer heterogeneity. Through this approach, it should be possible to carry out high-throughput drug screens and identify the best therapeutic strategy for individual patients with breast cancer.
Many studies on cancer genomics are conducted using information taken from biopsies, but Marco Gerlinger asked the question of whether a single biopsy is representative of the whole tumor. He presented results suggesting that this is not the case in renal cell carcinoma, and explained that tumor microheterogeneity has also been found in colon and stomach cancers. Gerlinger concluded that intratumor heterogeneity must be taken into account in precision medicine, recommending that new models based on evolutionary theory are needed to achieve better prediction of therapy response.
Targeted therapies in lung cancer: what’s next?
Since the discovery of EGFR, KRAS and ALK alterations in lung cancer, mutational analysis has been used to inform treatment strategies in the clinic. As explained by Tony Mok, the choice of targeted agent is important to ensure optimal outcome, and a number of studies are underway to investigate predictors of treatment success. One such predictor is the T790M mutation, a substitution in the gene encoding EGFR. Rolf Stahel presented the results of a study showing that the presence of T790M mutations is associated with better overall survival in patients with non-small cell lung cancer (NSCLC) treated with erlotinib and bevacizumab.
Alice Shaw highlighted that crizotinib, a tyrosine kinase inhibitor targeting ALK, is now standard first-line therapy for ALK-expressing NSCLC, but resistance rapidly develops via ALK-dependent or independent mechanisms. Shaw discussed the second- and third-generation ALK inhibitors under clinical investigation, concluding that the best sequence of targeted agents is yet to be determined. Solange Peters outlined other potential targets in lung cancer that have been identified through genomic analyses, including ROS, BRAF, HER2 and MET. Therapies targeting alterations in these genes could help to overcome resistance to ALK and EGFR-targeted agents, and Peters explained that existing targeted therapies could be beneficial to treat tumors with mutations in other genes due to off-target effects.
Together, these presentations showcased the growing number of mutations that could be targeted therapeutically in lung cancer, and suggested that specific genetic alterations could provide predictions of therapy response.
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