Expanded molecular testing improves lung cancer survival


More biomarkers should be included in the standard molecular testing for lung adenocarcinoma to improve patients’ prognosis and survival, results of the LCMC II (Lung Cancer Mutation Consortium II) study suggest.

“In addition to EGFR mutation and ALK rearrangement, we analyzed the frequency and clinical impact of a broader set of genetic alterations in lung adenocarcinoma. These include point mutations in AKT1, BRAF, ERBB2, KRAS, MAP2K1, PIK3CA and NRAS, as well as MET amplification, RET and ROS1 rearrangements, and PTEN and MET expression,” explained lead author Dr. Dara Aisner of the University of Colorado, CO, US. “Additional mutation data such as TP53 and PTEN were provided as available.” [ASCO 2016, abstract 11510]

A total of 875 patients with confirmed stage IV lung adenocarcinoma were recruited in this study. The patients were either prescribed standard treatment based on molecular testing results, or recommended to participate in clinical trial of agents specific for certain alterations.

The most frequent driver alterations in the study were KRAS mutation (25 percent), sensitizing EGFR mutation (10 percent) and ALK rearrangement (4 percent). AKT1 mutation was not detected, while other alterations were present in 0.5 to 3 percent of the studied population. “The remaining 44 percent had no detectable mutations by genotyping,” reported Aisner. “However, initial results from immunohistochemical analysis revealed MET expression and PTEN loss in 59 percent and 15 percent of the patients, respectively. The data are currently pending central review.”

“Smokers who carried detectable driver mutations had significantly longer overall survival [OS] than those who did not [median, 2.7 vs 1.6 years; p=0.008]. Therefore, identification of driver mutations is important in lung adenocarcinoma patients who have a smoking history,” she stressed. “In addition, KRAS mutations tended to be associated with a worse prognosis in never smokers.”

“Doubleton mutations were reported in 4.1 percent of the patients, with the majority having co-occurring MET amplification/KRAS mutation, PIK3CA/KRAS mutations, MET amplification/EGFR mutation or PIK3CA/EGFR mutations,” noted Aisner.

“TP53 mutations might confer a worse prognosis in patients harbouring sensitizing EGFR mutations who were treated with targeted therapy [median OS, 2.9 years vs not reached in counterparts without TP53 mutations; p=0.02],” she added. “TP53 mutations are likely under-reported, because the positivity rate was 48 percent by next-generation sequencing, but only 8 percent by non-next-generation sequencing in our study.”

Web App Ups Lung Cancer Survival by 7 Months


A web-based application that prompts lung cancer patients to complete a symptom chart weekly on a smartphone, tablet, or computer improved overall survival by 7 months, compared with standard follow-up care, according to results from a prospective phase 3 trial from France.

The key to the intervention is that it allowed “earlier detection of relapse” and, thus, early supportive care in the study patients, 90% of whom had stage III or IV disease, and all of whom had received previous first-line chemotherapy, said Fabrice Denis, MD, PhD, from the Institut Inter-regional de Cancérologie Jean Bernard in Le Mans, France.

“Relapse does not occur during a planned visit,” Dr Denis pointed out.

He spoke during a press conference here at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.

Dr Denis explained that the technology automatically triggers an email alert to the physician (which leads to a clinic visit) upon the detection of any anomaly in the data stream from the patient.

This system a “tremendous advance,” said Patricia Ganz, MD, a medical oncologist at the University of California, Los Angeles, who moderated the press conference.

“If we had a drug that provided this level of survival benefit, wouldn’t we want to go out and use it?” she asked.

In a multi-institutional, randomized trial, 60 patients used the app, known as Moovcare (Sivan Innovation), and 61 patients — the control group — received standard care, which was clinical routine assessment with a CT scan every 3 to 6 months, or at the investigator’s discretion.

Median overall survival was better in the app group than in the control group (19 vs 12 months). This translated into a 67% reduction in the relative risk for death (hazard ratio, 0.33; P = .0025).

The rate of 1-year overall survival was also better in the app group than in the control group (75% vs 49%); the absolute benefit was 26%. This was achieved despite the fact that the study was stopped early — at the planned 9-month interim analysis — because of positive benefit, and the control patients crossed over into the app group.

But the results need to be taken with a grain of salt, said study discussant Egbert Smit, MD, PhD, from the Netherlands Cancer Institute in Amsterdam.

The overall survival benefit was through delivery of appropriate treatment.

“We have to remember that the overall survival benefit was through delivery of appropriate treatment,” Dr Smit explained.

At relapse, more patients in the app group than in the control group received optimal therapy (74% vs 33%; P < .001). The exact therapies used were not indicated in the study data, he noted.
The disparity in optimal therapy at time of relapse was a reflection of patients in the app group maintaining a better performance status, which, in turn, was a reflection of the efficiency of the app in expediting clinical care, Dr Denis explained.

Despite reservations, Dr Smit called the app a “simple and clever tool,” and observed that there is no standard follow-up care after first-line therapy for lung cancer. He called for a confirmatory study.

This kind of “real-time interaction is already implemented at major centers,” said David Carbone, MD, a lung cancer specialist at the Ohio State University Comprehensive Cancer Center–James Cancer Hospital in Columbus.

For example, at Ohio State, cancer patients can call a 24-hour-a-day hotline staffed by a triage nurse, who interviews the patient and decides whether or not to contact a physician. Dr Carbone said he believes that “talking to a person may be preferred.”

The app, or similar technology, might be best when used in under-resourced settings and smaller practices, he told Medscape Medical News.

But Dr Ganz suggested that, in general, waiting for cancer patients to be forthcoming with their problems is not optimal.

“Systematically asking about things with a patient and asking them to respond [as the app does] is different than asking them, ‘How are you today? Are you having any problems?’ They won’t volunteer it,” she said.

The app requires that patients assess themselves weekly on 12 different measures, including asthenia, cough, dyspnea, and anorexia. Patients can also send a note through a text window.

The fact that the app requires patients to actively report their symptoms or complications is important, said Gregory Masters, MD, a lung cancer specialist at Christiana Care’s Helen Graham Cancer Center in Newark, Delaware, who served as an expert commentator at ASCO.

Lung cancer patients are often reticent about contacting their healthcare providers, he explained.

“Many of these patients have a lot of guilt about their diagnosis; we see that more in lung cancer patients than in many other patients,” he said. “Some patients do not want to bother the doctor, the nurse, or the healthcare team with their symptoms, or they think they are not important.”

During the press conference, Dr Masters pointed out that engaging patients is key to the outcome in this study, but is not exclusive to this specific app. “This study doesn’t show it is the only way or the best way [to improve survival].”

Dr Denis did not take offense at the comment. “You will have the same results if you call patients every week by phone,” he said.

It is not possible to follow many patients simultaneously [with the phone].
But that is impractical, he pointed out. “It is not possible to follow many patients simultaneously [with the phone].”

With the app, a clinician can spend 15 minutes a week following 60 patients, Dr Smit reported.

The benefits of timely intervention with the app were multiple.

There was a 50% reduction in imaging tests per patient per year in the app group, compared with the control group. And quality-of-life scores were higher in the app group.

Relapse rates were about 50% in both groups.

The Moovcare app is the first web-application for follow-up and early detection of relapses and complications for patients with advanced lung cancer, according to the Sivan Innovation website. The technology has a patent in the United States and Europe, and is currently undergoing a CE marking procedure in Europe. The company is developing the app for 15 other indications in oncology, including lymphoma. The latter project is being conducted in partnership with Takeda France.

Dr Carbone should be pleased. He believes that technology is not fully tapped in terms of healthcare applications. “The more that these intelligent data captures become readily available, the more everyone benefits,” he said.

Statins Linked to Improved Lung Cancer Survival


Mortality modestly lower for statin users in observational study..

Sustained statin use was associated with modestly better survival in lung cancer, an observational study in Great Britain showed.

People already on statins before diagnosis had a hazard ratio of 0.88 for lung cancer–specific mortality compared with other lung cancer patients after adjustment for various factors (P<0.001), Chris Cardwell, PhD, of Royal Victoria Hospital in Belfast, Ireland, and colleagues found.

Use after diagnosis was associated with a similar adjusted hazard ratio of 0.89 for lung cancer–specific mortality, albeit not statistically significant at P=0.09, the group reported in the May issue ofCancer Epidemiology, Biomarkers & Prevention.

That association was stronger after 12 prescriptions (adjusted HR 0.81, P=0.03) and when limited to lipophilic statins (adjusted HR 0.81, P=0.01), particularly simvastatin (Zocor), although attenuated in some sensitivity analyses.

Although these “associations could be causal or could reflect residual confounding or other biases,” the researchers pointed out “preclinical evidence for anticancer properties of statins from lung cancer cell lines and mouse models.”

Observational studies have also linked statins to better cancer-specific mortality in breast, prostate, and colorectal cancers.

“These results require confirmation in further large epidemiologic studies, particularly those with complete stage data, which could inform the decision to conduct a trial of simvastatin in lung cancer patients,” Cardwell’s group concluded.

Their study included 3,638 newly-diagnosed lung cancer patients in the English cancer registry from 1998 to 2009, linked to prescription records in the U.K. Clinical Practice Research Datalink and national mortality data up to 2012.