Christina Izzo

A new study has found that a psychosocial telephone counseling intervention helps improve mood and quality of life in cervical cancer survivors.

, show that a psychosocial telephone counseling intervention benefits mood and quality of life, including  cancer-specific and gynecologic concerns for this population of patients.

&ldquo;What our work has determined over the years preceding this trial was that women with cervical cancer in particular are one of the most distressed group of cancer survivors, if not the most in the United States,&rdquo; lead author Lari Wenzel, PhD, Associate Director for Population Science and Cancer Control at the University of California, Irvine Chao Family Comprehensive Cancer Center, said in a recent phone interview with

. &ldquo;Also, this is a group who may not get the amount or type of supportive care services that could be beneficial.&rdquo;

Many cervical cancer patients are often young and underserved minorities, said Wenzel, who is also a professor of Medicine and Public Health at the UCI School of

. Survivors of the disease often face quality of life disruptions that can linger for long periods of time after treatment has ended, such as sexual and childbearing functioning concerns.

Wenzel said the idea of testing a telephone counseling intervention made sense in this situation because these patients are &ldquo;a group that don&rsquo;t avail themselves of typical services such as a support group at a hospital or elsewhere.&rdquo;

For the study, 204 patients who were &ge;9 months and <30 months from diagnosis were randomized to receive the telephone counseling service or usual care.

The psychological telephone counseling intervention included five weekly sessions and a 1-month booster. Patients reported outcomes at baseline and 4 and 9 months after enrollment.

The participants in the telephone-counseling group received a 5-minute pre-call to schedule the first session, which took up to 60 minutes. The rest of the sessions ranged from 20 to 60 minutes and included topics on managing stress and emotions, health and wellness, managing relationships and sexuality concerns, and communicating with the health care team.

After each session, the counselor would prepare a summary letter of the session along with &ldquo;homework&rdquo; assignments to help the patient overcome stresses or concerns that they had talked with the counselor about.

Wenzel said one of the benefits of this strategy was that even though the counselors talked about general themes around areas that cancer survivors find important, the homework assignments allowed the treatment to be tailored for each individual.

The study also looked to see if there was an association between quality of life and biomarkers.

Interestingly, the study found a correlation between the improvement in patient-reported outcomes and a decrease in both T-helper type 2 (TH-2) and counter-regulatory cytokines.

&ldquo;We know that in individuals that experience chronic psychological stress, their immune system tends to shift a bit, its &ldquo;immunological stance&rdquo;, to try to make more antibodies to keep the body from getting an infection rather than having an immune system that is ready and primed to fight the infection once it arrives. We call that a T-helper type 2 or TH-2, response,&rdquo; study author Edward L. Nelson, MD, FACP, Chief of the Hematology/Oncology Division and Associate Professor of Medicine, Molecular Biology & Biochemistry, at the University of California, Irvine said in an interview.

&ldquo;So under chronic psychological stress, the amount of TH-2 is much higher than it is when you don&rsquo;t have that chronic psychological stress. TH-1 and TH-2 can be thought of as being on opposite sides of a seesaw. TH-1 responses are thought to be best for fighting cancers and virus infections. If you have a whole bunch of TH-2, you have less TH-1.&rdquo;

The study found that women who had improvement in the quality of life and a decrease in their stress level also saw a decrease in TH-2.

&ldquo;This study reinforces a paradigm that connects the psychological state to downstream effects on the neuroendocrine and immune systems, the immune system in particular,&rdquo; he said. &ldquo;If you&rsquo;re going to ask the immune system to behave in the way that you would like it to behave, to fight off cancer, especially with some of our other now novel immunotherapeutic strategies, you would like it to be tuned up in a way that makes it most likely that it is going to be effective.&ldquo;

Even though the study didn&rsquo;t explore whether a decrease in TH-2 resulted in either longer control of a tumor or improved survival, stress raises TH-2, which is associated with decreased magnitude of TH-1.

&ldquo;Under situations of chronic psychological stress, the immune system is&hellip;not tuned up for fighting off tumors,&rdquo; Nelson continued. &ldquo;And so, as we start to think about ways to tap into the immune system for fighting off cancer, we would do well to think about how we can address the psychological state to help our immune system be tuned up to do the best job that it can.&rdquo;

The study found that survivors receiving the psychosocial telephone counseling intervention had significantly improved depression and gynecologic and cancer-specific concerns at 4 months compared with those who only received usual care (

< .05) and the significant differences in gynecologic and cancer-specific concerns were sustained at 9 months.

Based on these data, Wenzel said there&rsquo;s plenty that oncology nurses can take away and even use in practice.

&ldquo;I know that [oncology nurses] are already sensitive to the psychosocial issues of cancer patients,&rdquo; she said. &ldquo;But I think that they can look at this cancer population and if they start out by saying &lsquo;Well, this is a population that is particularly in need of supportive care efforts,&rsquo; and it&rsquo;s not one-size-fits-all, but [nurses] might be able to have a conversation to be able to understand the issues that these women are facing in such a way that this conversation and a follow-up care plan could be very helpful for the patient.&rdquo;

&ldquo;I think the other thing that oncology nurses can take away is the understanding that these women are going to have some rather profound stressors and disruption of their quality of life,&rdquo; Nelson said. &ldquo;So lots of times, having our patients know what&rsquo;s coming and knowing that there are other resources that are available to help them is a way, in and of itself, to decrease the distress.&rdquo;

Looking forward, Wenzel said she believes that these patients would benefit from booster or maintenance sessions, to help the patients continue their progress.

&ldquo;This could be extremely cost effective if we&rsquo;re helping people long-term,&rdquo; she said. &ldquo;But this is something we need to test to see if we can help people long term.&rdquo;

Some changes might need to be made to the counseling service, too, Wenzel said.

Data showed that those with higher depression in the telephone intervention arm were significantly more likely to drop out of the study. In order to combat this in the future, Wenzel said she plans to make the first session more interactive.

&ldquo;Some of the questions that we were asking were quite probing in terms of level of depression, sexual dysfunction, relationships, interactions with the healthcare team, and you can imagine if you&rsquo;re already experiencing a level of depression that&rsquo;s rather profound, sometimes actually people just want to turn inward and don&rsquo;t want to talk about it,&rdquo; she said. &ldquo;So I think what I would do differently in our session 1 is to be sensitive to those presumed issues and allow the counselor and the patient to develop a relationship at a pace that the patient is optimally comfortable with.&rdquo;

The intervention also has the potential to be brought into the clinic, Wenzel said. And implementing the intervention closer to the time of diagnosis may help improve stress and quality of life earlier, with potential long term benefits as well.

&ldquo;Since this [study] has been published, we&rsquo;ve heard from many physicians who have said they would appreciate help with this population,&rdquo; she said.

The intervention also has the potential to be tested as a web-based intervention or more closely integrate technology, such as email or text messaging. This intervention can also be tested among other cancer survivors, Nelson said.

&ldquo;There are other patient populations besides women with cervical cancer and cervical cancer survivors who also have fairly profound disruptions in their quality of life,&rdquo; he said. &ldquo;So we&rsquo;d like to be able to know if this same strategy can be applied to those patient populations.&rdquo;

Articles

Improving Quality of Life in Cervical Cancer Survivors

Prior cancer history should not exclude patients with advanced lung cancer from participating in clinical trials because it does not impact outcomes, according to a study. The study, led by researchers at the UT Southwestern Medical Center, could help boost enrollment in lung cancer clinical trials.

&ldquo;When it comes to clinical trial eligibility, a history of prior cancer should not count against you,&rdquo; senior author David Gerber, MD, said in a statement. &ldquo;For patients with advanced lung cancer, previous cancer does not adversely affect survival, regardless of the type, stage, or timing of the prior cancer.&rdquo;

The NCI estimates that more than 14 million people in the United States have a history of cancer, but there are currently fewer than 5% of adults with cancer participating in clinical trials here.

Gerber, associate professor of Internal Medicine, Division of Hematology and Oncology, at the Harold C. Simmons Comprehensive Cancer Center, said that up to 18% of lung cancer patients are excluded from clinical trials solely based on the fact that they have a history of prior cancer.

&ldquo;This longstanding and widespread practice reflects concerns that lung cancer patients with a prior cancer would have worse outcomes,&rdquo; he said. &ldquo;In the current study, these patients&rsquo; outcomes were as goodor even better&mdash;than those with no previous cancer diagnosis.&rdquo;

For the study, which was published in the Journal of the National Cancer Institute, researchers analyzed 102,929 patients over the age of 65 who were diagnosed with stage IV lung cancer between1992 and 2009. Of these patients, 14.7% had a history of prior cancer.

Of those with a prior cancer, 76% were diagnosed at stages I, II, or III, and most were diagnosed less than 5 years prior to their lung cancer diagnosis. Among women analyzed in the study, the most common prior cancers were breast, gastrointestinal, and gynecologic whereas the most common prior cancers for men were prostate, other genitourinary cancers, and gastrointestinal cancers.

The study found that patients with prior cancer had 10% overall survival and 20% better lung cancerspecific survival than those with no previous cancer diagnosis.

Researchers hypothesized that the reason prior cancer patients had superior survival has to do with a lead-time bias rather than a biologic advantage.

&ldquo;The clinical and radiographic surveillance related to the prior cancer may result in earlier diagnosis of the stage IV lung cancer. This shift leads to longer documented survival times,&rdquo; said Gerber.

Nonetheless, the knowledge from this study provides key data to help change clinical trial enrollment.

&ldquo;Modifying the policy for clinical trial inclusion could lead to faster accrual of patients, higher trial completion rates, and more generalizable trial results that can help a greater number of patients, ultimately leading to better treatments,&rdquo; coauthor Ethan Halm, MD, chief of the William T. and Gay F. Solomon Division of General Internal Medicine, and chief of the Division of Outcomes and Health Services Research in the Department of Clinical Sciences at UT Southwestern, said in a statement.

Laccetti AL, Pruitt SL, Xuan L, et al. Effect of prior cancer on outcomes in advanced lung cancer: implications for clinical trial eligibility and accrual [published online February 9, 2015]. J Natl Cancer Inst. doi:10.1093/jnci/djv002.

Prior cancer history should not exclude patients with advanced lung cancer from participating in clinical trials because it does not impact outcomes, according to a study.

Study Findings Could Help Boost Lung Cancer Trial Enrollment

Recent advancements in the treatment of ovarian cancer, including the approvals of bevacizumab and olaparib, have led the National Comprehensive Cancer Network to make changes to their clinical practice guidelines in its 20th annual edition.

"There have been a number of advancements in the treatment of ovarian cancer since the first NCCN Guidelines were published in 1996," Robert J. Morgan Jr, MD, FACP, professor of medical oncology, Department of Medical Oncology and Therapeutics Research, City of Hope, and Chair, NCCN Guidelines Panel for Ovarian Cancer, said in a statement. &ldquo;One major development is the recommendation for intraperitoneal chemotherapy in certain patient populations. Now a category 1 designation, this treatment recommendation was added to the Guidelines when strong evidence was published that showed this treatment approach to have a major improvement on the median survival in women."

Guideline changes were also made to sections referring to treating epithelial ovarian cancer, Fallopian tube cancer, and primary peritoneal cancer; less common ovarian histopathologies; malignant germ cell tumors; ovarian low malignant potential tumors; malignant germ cell and sex-stromal tumors; and to the International Federation of Gynecology and Obstetrics Guidelines of staging classification for ovarian cancer, Fallopian tube cancer, and peritoneum cancer.

The combined analysis of the GOG-172 and GOG-114 trials showed that patients treated with IP experienced a 16% reduction in the risk of progression compared with IV therapy. Additionally, IP chemotherapy led to a median overall survival (OS) of 62 months compared with 51 months for IV therapy.

However, this combination regimen causes more side effects than IV chemotherapy alone. Researchers are continuing to study lower doses and alternative drug approaches to try to produce similar benefits with fewer side effects.

Surgery surrounding ovarian cancer has also improved over the years, said Morgan, who has served as the NCCN Guidelines Panel Chair for Ovarian Cancer for 20 years.

In the guidelines&rsquo; original version, he explained, there was marked disagreement regarding the role of complete surgical staging in low-stage cancer with a category III recommendation.

"Since that time, the role of surgery has become clearer, and complete surgical staging and/or debulking is now recommended for virtually all patients who are suspected of having any residual disease,&rdquo; Morgan said.

European studies have demonstrated that upfront cytoreductive surgery is associated with a survival advantage compared with cytoreductive surgery after three cycles of chemotherapy.

Another significant update in the field of ovarian cancer was the November 2014 approval of bevacizumab (Avastin) in combination with chemotherapy for patients with platinum-resistant recurrent ovarian cancer.

&ldquo;Avastin plus chemotherapy is the first new treatment option for women with this difficult-to-treat type of ovarian cancer in more than 15 years,&rdquo; Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said at the time of the approval. &ldquo;Risk of the disease worsening was reduced by 62% for women who received Avastin plus chemotherapy in the study, and a notable treatment effect was observed with paclitaxel, which may be important when choosing treatment.&rdquo;

The FDA approval was based on the phase III AURELIA trial, which demonstrated a median progression-free survival (PFS) with bevacizumab of 6.8 versus 3.4 months with chemotherapy alone (HR = 0.38;

Because improvement in PFS rather than OS may be an acceptable treatment outcome, explained Morgan, bevacizumab-containing regimens are listed; however, these regimens may have differing category 2A, 2B, or 3 recommendations due to the strength of published evidence showing an improvement, depending on when in the course of treatment the regimens are used.

The guidelines were updated to also include olaparib (Lynparza), which was approved in December 2014. The PARP inhibitor is approved to treat patients with

-positive advanced ovarian cancer following treatment with three or more cycles of chemotherapy.

The FDA approval was based on a single-arm phase II study, which demonstrated a 34% objective response rate (ORR), with a 7.9-month duration of response, seen in 137 patients.

"NCCN is proud to have played a role in the advancement treatment of women with ovarian cancer since the first NCCN Guidelines were published in 1996," Robert W. Carlson, MD, chief executive officer, NCCN, said in a statement. "We applaud Dr. Morgan and panel for their decades of service and dedication to improving the outcomes for women with such a deadly disease."

Recent advancements in the treatment of ovarian cancer have led the National Comprehensive Cancer Network to make changes to their clinical practice guidelines in its 20th annual edition.

New Ovarian Cancer Guidelines Include Bevacizumab, Olaparib Approvals

The &ldquo;Precision Medicine Initiative&rdquo; that was briefly mentioned by President Barack Obama during his State of the Union Address last week will require a $215 million initial investment, with the goal of discovering cures for diseases such as cancer and diabetes.

&ldquo;We have the possibility of leading an entirely new era of medicine that makes sure that new jobs and new industries and new lifesaving treatments for diseases are created right here in the United States,&rdquo; the President said.

The President&rsquo;s 2016 budget request will include $215 million for the National Institutes of Health (NIH), the FDA, and the National Coordinator for Health Information Technology (ONC), to support and foster the goals of precision medicine.

The administration will provide $70 million of the funds to the National Cancer Institute (NCI), part of NIH, to scale up efforts to identify genomic drivers in cancer and apply that knowledge in the development of more effective approaches to cancer treatment.

&ldquo;We want to use that knowledge to develop new and more effective approaches to help people beat this disease,&rdquo; the President said.

President Obama also mentioned that the administration would work together with the FDA to develop new approaches for evaluating next generation genetic tests by approving $10 million to acquire additional expertise.

&ldquo;The way we approve a new gene sequencing technology is going to be different than the way we approve a new pacemaker or prosthetic device,&rdquo; he said.

The NIH will receive $130 million to develop a voluntary national research cohort of 1 million or more volunteers to propel our understanding of health and disease and set the foundation for a new way of doing research through engaged participants and open, responsible data sharing.

&ldquo;Just like analyzing our DNA teaches us more about who we are than ever before, analyzing data from one of the largest research populations ever assembled will teach us more about the connections between us than ever before,&rdquo; he said.

The administration will also make sure that patient privacy remains a top priority, he stressed.

The ONC will receive $5 million to support the development of interoperability standards and requirements that address privacy and enable secure exchange of data across systems.

The President mentioned that patient&rsquo;s rights advocates will be hands-on in assisting with designing this part of the initiative.

He also called on hospitals, researchers, and privacy experts to join in the initiative and for entrepreneurs and nonprofits to help create tools &ldquo;that give patients the chance to get involved as well.&rdquo;

&ldquo;Because we want every American ultimately to be able to securely access and analyze their own health data so that they can make the best decisions for themselves and for their families,&rdquo; the President said. &ldquo;This has the possibility of not only helping us find new cures, but it also helps us create a genuine healthcare system as opposed to just a disease care system.&rdquo;

And while every investment doesn&rsquo;t always pan out, every $1 spent on the Human Genome Project so far, which helps support the innovation of precision medicine, has already returned $140 to the economy.

&ldquo;There&rsquo;s a huge economic stake in us tapping in to this innovation,&rdquo; the President said. &ldquo;But as anyone who has watched a loved one battle with an illness, particularly a life threatening illness . . . the most important impact these investments can have can&rsquo;t be measured in dollars.&rdquo;

President Obama went on to say that precision medicine &ldquo;gives us one of the greatest opportunities for new medical breakthroughs that we have ever seen.&rdquo;

And for a small subset of patients, the promise of precision medicine is already here.

Physicians and researchers have realized for some time now that a &ldquo;one-size-all&rdquo; approach wasn&rsquo;t going to work anymore. And in the field of cancer, a growing understanding of the disease and accompanying genetic mutations have led to earlier detections and more targeted therapies to treat certain cancers.

&ldquo;We live in an extraordinary time when the scientific opportunities and our ability to translate this new knowledge into ways to both save and improve the quality of life of patients are simply astounding,&rdquo; Margaret Foti, PhD, MD (hc), chief executive officer of the American Association of Cancer Research, said in a statement. &ldquo;This is why we are so excited about today&rsquo;s event at the White House and specifically about President Obama&rsquo;s major investment in the enormous potential of precision medicine, which is in the very early stages of transforming health care.&rdquo;

Advances in these technologies mean that the breakthroughs we&rsquo;ve already made are just the beginning, the President said.

When Francis S. Collins, MD, PhD, the director of the NIH, first sequenced the first human genome, it cost about $100 million. Now, it costs less than $2000, the President said.

But behind the cost, is the real goal the President said:

&ldquo;We&rsquo;re here to harness what is most special about America, and that is our spirit of innovation, our ability to dream, to take risks, to tinker and try new things. And as a result of that, not only improve our economy, but improve the lives of men and women and children of generations to come.&rdquo;

But even with costs lowering for genomic testing, integrating those tests and results into practice is still going to take time.

&ldquo;With whole genome or whole exome testing, you can go into the test with one goal in mind, but more information is gathered on other health risks as a result of the test,&rdquo; Joy Larsen-Haidle, MS, CGC, a genetic counselor at the Humphrey Cancer Center and the President of the National Society of Genetic Counselors , said in a phone interview.

&ldquo;It&rsquo;s going to be really important for patients to understand what the test is going to tell them, how they&rsquo;re going to use it in their medical care, and to participate in that informed consent process so that they&rsquo;re ready to hear that information.&rdquo;

Haidle feels that there are changes that can be done now that can help impact access to genetic services.

&ldquo;Some of the things that we might think about today are how do we improve access to genetic experts, such as a genetic counselor,&rdquo; she said. &ldquo;One of those ways, from our perspective, is if we can get genetic counselors recognized as providers under CMS, that decreases an access barrier for our senior citizens and also for some other patients that are covered by a third-party payer.&rdquo;

Haidle said there is also a need for standardization of how much family history is collected and better utilization of electronic medical records to help physicians and providers keep track of family history.

And with studies showing that some physicians are uncomfortable with ordering genomic testing because they do not know how to interpret the results, practices are going to have to start developing a more team-based approach that includes genetic counselors.

The â€œPrecision Medicine Initiativeâ€ that was briefly mentioned by President Barack Obama during his State of the Union Address last week will require a $215 million initial investment, with the goal of discovering cures for diseases such as cancer and diabetes.


Precision Medicine Initiative Requires $215 Million Initial Investment

Details about an experimental treatment option for patients with squamous cell non-small cell lung cancer (NSCLC) were presented at the 2014 European Society for Medical Oncology (ESMO) Congress. Suresh S. Ramalingam, MD, presented preliminary data from a randomized, phase II trial that demonstrated an improvement in outcomes with the combination of the poly (ADP-ribose) polymerase (PARP) inhibitor veliparib and chemotherapy in patients with this hard-to-treat histology.

In the study, progression-free survival (PFS) was improved by 35% and overall survival (OS) was extended by 30% with the combination of veliparib and chemotherapy in patients with previously untreated metastatic or advanced NSCLC. In patients with squamous histology, PFS was 6.1 months with veliparib compared with 4.1 months (hazard ratio [HR] = 0.50;

= .06) and the OS was 10.3 months with veliparib compared with 8.4 months (HR = 0.71;

Peter Hammerman, MD, PhD, Discusses the Future of the Treatment of Squamous Cell Lung Cancer

Hammerman is an assistant professor of medicine at Harvard Medical School.

Q: How was it discovered that veliparib had utility in lung cancer?

Ramalingam, a professor of medical oncology at the Winship Cancer Institute of Emory University in Atlanta, Georgia, discussed the results of the trial and the potential of veliparib as a treatment for patients with squamous cell NSCLC in an interview with

PARP is a protein that&rsquo;s involved in DNA repair and veliparib is a very potent inhibitor of PARP1 and PARP2. Basically, when you give a PARP inhibitor, the cell is not able to repair DNA damage effectively. What we&rsquo;ve seen in the past is if the cells have deficiency in homologous recombination repairs, which is what happens in

gene mutations, those cells become far more dependent on the basic repair pathway, which is exactly where the PARP comes into play, even though the role of PARP is well known beyond that.

So by blocking DNA in cells that are critically dependent on that pathway, you are able to induce lethal damage. In lung cancer, if you look at what the common modalities of treatment are, we use platinum compounds, which are the cornerstones of therapy, and then we use radiation, and both of these work by inducing DNA damage. Cells that can repair the DNA damage end up not being sensitive to radiation or chemotherapy with platinum-based regimens.

Q: What were the findings from this phase II trial?

We and other labs have been studying the combination of chemotherapy with PARP inhibition, and veliparib in particular, and they have shown that veliparib is associated with increased efficacy when it is combined with chemotherapy or radiation. That was the basis for our clinical evaluation of veliparib in combination with platinum-based chemotherapy.

This was a randomized, placebo-controlled trial where we enrolled patients with previously untreated NSCLC, [as] first-line therapy for metastatic disease, and patients were randomized 2:1 to get carboplatin and paclitaxel with either veliparib or placebo. The veliparib was given for the first 7 days of each cycle, chemotherapy was given on day 3, veliparib was given from days 1 through 7, and the reason we used this strategy was because we wanted to prime the cells with PARP inhibition and then introduce chemotherapy.

Patients were allowed to continue the treatment for a maximum of 6 cycles, there was no maintenance therapy involved, and the primary endpoint for this was PFS. We also looked at OS, objective response rates, and the safety of the regimen as secondary endpoints.

Of a total 158 patients, 105 [were] randomized to the experimental arm with veliparib and 53 patients were enrolled to the control arm with chemotherapy and placebo. In this trial, the baseline characteristics were evenly matched and the main stratification factors were histologyeither squamous or nonsquamous&mdash;and smoking status&mdash;never versus current versus past. The randomization resulted in equal distribution of histology and smoking status across the 2 arms.

As far as safety, we found that the combination was tolerated really well. There were no toxicities that occurred more frequently with veliparib-chemotherapy compared to chemotherapy alone with placebo. Some of the common toxicities that you would see with chemotherapy, like neutropenia, thrombocytopenia, or anemia, were very similar between the 2 arms of the trial. Grade 1/2 toxicities were also very similar. Notably, there was no evidence of more nausea, vomiting, or fatigue with the addition of veliparib to chemotherapy.

When we look at efficacy, the overall primary endpoint, PFS, was 4.2 months median in the control arm and 5.8 months median with veliparib (HR = 0.74). The OS was 9.1 months in the control arm compared with 11.7 months in the veliparib arm. These differences, while clinically meaningful, did not reach statistical significance.

When we look at specific histologies, we found the most exciting data. In squamous histology, the median PFS improved from 4.1 months to 6.1 months with veliparib. In nonsquamous, we did not see a significant difference.

The OS results also mirrored what we saw with PFS. The squamous group had a median OS of 8.4 months with chemotherapy alone and 10.3 months with the combination. These results suggest that the squamous group had the best benefit with the combination.

Another observation that we noted was the response rate, which was very similar between the control and the experimental arm. However, the duration of response was almost 2-fold higher with the addition of veliparib (3.3 months to 6.9 months). What this tells us is that patients whose tumors were sensitive to platinum-based therapy experience an even better response and a longer duration of response with the addition of veliparib.

Q: Can you speculate why the patients with squamous histology responded better to the therapy?

Q: Could veliparib ever be used as monotherapy or combined with agents other than chemotherapy in the future?

Essentially, the results showed that the combination of veliparib with carboplatin and paclitaxel is particularly more efficacious to squamous histology and that is the histologic subtype we are going to be moving into a phase III trial. In fact, a phase III trial is already under way.

At this point, it&rsquo;s hard to say exactly the reasons behind that. We&rsquo;re still trying to understand the differences. We know that DNA repair capacity may depend on histologic subtype but this is something that we are obviously looking into more carefully.

There is certainly room for additional novel combination regimens. As monotherapy in lung cancer, we don&rsquo;t think veliparib is going to be an effective agent unless, of course, we identify potentially a group of patients who have low

function, not mutation. That&rsquo;s a group that&rsquo;s not particularly a high proportion and we haven&rsquo;t done much work in that group with any drug, for that matter. In terms of novel combinations, there are increasing possibilities. We are beginning to understand more and more the role of PARP in similar functions beyond DNA repair and that paves the way for a variety of combinations that one could think about beyond chemotherapy.

Q: What are some of the challenges in treating lung cancer, and how would veliparib, if approved, help overcome those challenges?

What is really interesting is the combination with radiation, where we are seeing very interesting preliminary preclinical observations and, therefore, trials are looking at veliparib in combination with radiation in stage III lung cancer patients.

: Lung cancer is a very heterogeneous disease. In the setting of targeted therapies, we&rsquo;ve seen that adenocarcinoma patients have a number of driver mutations and, therefore, specifically targeted drugs are being studied for them. In squamous cell, we don&rsquo;t have any targeted drug that has been approved by the US Food and Drug Administration (FDA) for treatment and this is very much a patient population that is looking for new ways to treat them. We feel that if the phase II results can be confirmed in a phase III trial, veliparib can be an important component of treating squamous-cell cancer in the first-line setting. Squamous cell patients are 20% to 25% of all our patients with lung cancer in this country and even a bigger proportion in Europe and other countries.

Suresh S. Ramalingam, MD, discussed the potential of veliparib as a treatment for patients with squamous cell NSCLC in an interview with Targeted Oncology.

Veliparib Shows Potential in Squamous Cell NSCLC

New research has identified a genetic variant that helps reduce the risk of breast cancer in some Latina patients by 40% to 80%.

and conducted by researchers at University of California, San Francisco, showed that the variant, a difference in just one of the three billion &ldquo;letters&rdquo; in the human genome known as a single-nucleotide polymorphism (SNP), originates from indigenous Americans and confers significant protection from breast cancer. This protection is particulary significant in the more aggressive estrogen receptornegative forms of the disease, which generally have a worse prognosis.

&ldquo;The effect is quite significant,&rdquo; Elad Ziv, MD, professor of medicine at UCSF and senior author of the study, said in a statement. &ldquo;If you have one copy of this variant, which is the case for approximately 20% of US Latinas, you are about 40% less likely to have breast cancer. If you have two copies, which occurs in approximately 1% of the US Latina population, the reduction in risk is on the order of 80%.&rdquo;

Epidemiological data have long demonstrated that Latina women are less susceptible to breast cancer than women of other ethnicities. According to National Cancer Institute data from 2007 to 2009, whites have about a 13% lifetime risk of breast cancer, blacks about 11%, and Hispanics less than 10%. The lifetime risk among Hispanics with indigenous American ancestry is even lower.

The researchers performed successive genome-wide association analyses of datasets from the Cancer Prevention Institute of California (CPIC) and a study known as the Multiethnic Cohort. They replicated their initial findings in data from the Women&rsquo;s Health Initiative study, from a study of breast cancer in Colombian women known as COLUMBUS, and from a study conducted in Mexico, ultimately incorporating DNA data from a total of 3140 women with breast cancer and 8184 healthy controls.

The newly discovered SNP is on chromosome 6, near a gene coding for an estrogen receptor known as ESR1. While the biological basis of the association between the variant and reduced breast cancer risk is still not known, preliminary experiments indicate that the variant interferes with the action of transcription factors, proteins that regulate the expression of the ESR1 estrogen receptor.

The study also found that women who carry the variant have breast tissue that appears less dense on mammograms. Previous research has shown that high mammographic density is a risk factor for breast cancer.

&ldquo;We have detected something that is definitely relevant to the health of Latinas, who represent a large percentage of the population in California, and of other states such as Texas,&rdquo; first author Laura Fejerman, PhD, assistant professor of medicine and a member of UCSF&rsquo;s Institute of Human Genetics, said in a statement. &ldquo;This work was done as a collaboration of multiple investigators, many of us originally from Latin America. As a Latina myself, I am gratified that there are representatives of that population directly involved in research that concerns them.&rdquo;

&ldquo;If we can use these results to better understand how this protects estrogen receptor-negative breast cancer, that would be interesting and important,&rdquo; Ziv said, &ldquo;because right now we have no good way to prevent that type of breast cancer.&rdquo;