AACR update: New immunotherapy drug shows benefit in lung cancer


Debu Tripathy blog image

One of the areas that has progressed quite a bit recently is that of tumor immunotherapy. At this year's annual meeting of the American Association for Clinical Research, several papers have been presented in this area.

One of the most exciting is advances in lung cancer, which has been a traditionally hard to treat cancer. Recently there have been newer targeted therapies that work against growth factor receptors that show benefit, particularly in non-smokers. And now we're seeing advances in immunotherapy.

Now, a fundamental breakthrough in immunology has come with understanding the controls of the immune cells that allows us augment the natural immune response that white cells have against tumors.

One of the proteins blocked is the PD-1 receptor and PD-1 ligand. These proteins are important because the cancer cells can use them to block the immune system from attacking the cancer. There are several drugs being tested that inhibit this blockade, the so-called immune checkpoint, in trials not only for lung cancer, but also melanoma and other solid tumors.

One of the potential benefits of one of these drugs called MK-3475 is that it may work in people who have a history of smoking, people who have traditionally not benefited from these targeted therapies.

There is also some new information that we may be able to identify patients who have the best chance of responding to these drugs. There will be a more formal comparison and information on how the drug works in smokers coming hopefully very soon. We expect to hear those results at the annual ASCO meeting this summer.

Debu Tripathy is an oncologist and editor-in-chief of CURE. He is the co-leader of the Women's Cancer Program at Norris Comprehensive Cancer Center and Professor of Medicine at the Keck School of Medicine at the University of Southern California.


Do you understand the goal of your cancer treatment?


The New England Journal of Medicine tends to publish larger and higher impact studies that will affect standards of care, but they also will print eye-opening studies that tell us something unexpected and give us pause for thought.

A very important survey appeared in the Journal recently – it was part of a larger study that explored the attitudes and knowledge of patients with colorectal and lung cancer. This analysis of patients with advanced metastatic cancer who opted for chemotherapy showed that most patients had unrealistic expectations of cure – something that is rare in metastatic cancer. This is in contrast to earlier studies, many of which were done at larger and specialized cancer centers, which showed that most patients understood that cure was not likely.

What does this study say about patients being seen in clinical practice that reflects the average across the United States? At initial glance, it appears that patients are not adequately informed or do not fully understand their accurate prognosis. However, it is difficult to interpret results of questions asked or over the phone and to surrogates who answer in the patient's stead as was the case in this study. This study was not designed to delve into the complexities of patients' levels of hopes and understanding about their disease. Still, there are important lessons for us all in these results.

A higher expectation of cure was seen in patients who were non-white, or had colorectal cancer, and interestingly, who reported better communication with their physician. It means that physicians need to use better educational methods, but still retain their patients' trust and confidence. We live in a time where technology keeps pushing the envelope on outcomes in cancer, but where cure of many common cancers in the metastatic setting is still fleeting. The public needs to make fully informed decisions about their health care – whether it is for metastatic cancer or open heart surgery for coronary artery disease.

In this age of information at one's fingertip, this should be much more achievable, but on the other hand, the savviest of readers needs a guide in the informational jungle. CURE's special edition on metastatic cancer, which will be available in December, aims to educate with compassion, realism and hope – we believe that all of these are mutually compatible.


Drug approvals: Are we in a new age yet?


With all the news of cancer drug shortages and the FDA's controversial decision to withdraw approval of Avastin (bevacizumab) for breast cancer, we are also getting some positive developments.

Just recently (on Aug. 26), the FDA granted accelerated approval to Xalkori (crizotinib), the newest member of an emerging generation of "niche" drugs. These are drugs that work in very defined subsets of patients, based on certain biological characteristics.

In the case of Xalkori, this is confined to the approximately 3 to 9 percent of patients with non-small cell lung cancer (NSCLC) who carry a chromosomal translocation that results in overexpression of the ALK protein (anaplastic lymphoma kinase). In fact, the approval of this drug is accompanied by the approval of a gene-based test to detect this translocation in tumor tissue. This approval comes on the heels of the approval of Zelboraf (vemurafenib) just eight days earlier for advanced melanoma, and again, only for the subset who harbor a mutation in the BRAF gene, and also approved with a diagnostic kit called the cobas 4800 BRAF V600 Mutation Test. In this case, the mutation is more common, seen in about half of all melanomas.

The big question is whether these two approvals herald the new age of personalized drugs. The now old story of Herceptin that many regard as one of the first targeted therapies, was spread out over 17 years from discovery of the gene to drug approval (or 11 years if you go from the discovery of HER2 amplification in breast cancer).

The new generation of drugs is being developed in a just a few years based on our exponentially growing body of data on mutations carried in cancers and new clinical trial designs that rapidly test drugs and verify biomarkers that predict response. Moreover, they seem to be quite effective with a higher percentage of patients responding, but not to the point that permanent cures are expected.

One can only hope that we are truly in the new era – and there are several indicators that this is the case. The Cancer Genome Atlas (TCGA) program is one of several worldwide that is collaboratively sequencing tumor genomes. Drug companies are investing more effort into biomarker analyses and integrating them earlier in the clinical trial process. Healthcare reform is demanding that drugs have a larger impact and that they not be used indiscriminately. Finally, the public's expectations are rising – they want more information about their cancers and access to clinical trials.

While it is possible that the initial wave of "low-hanging fruit" of "druggable" gene targets will soon be exhausted, it is more likely that we will have more targets and drugs than we can test. The bottleneck will really be in the patient clinical trials and how quickly and widely they can be deployed and fully enrolled. There will still be negative trials and other disappointments, but perhaps we are entering a new era where the bar of success is being raised.