For our last #LCSM tweet chat of the year, this Thursday, December 18th at 8 PM ET/5 PM PT, we’ll do a retrospective reflection on the biggest developments of 2014. It was a pretty good year for lung cancer, so I’ll offer up my view of the top 5 changes over the past year and welcome group discussion on whether these fall in line for others.
Dr. West’s Top 5 Highlights in 2014
1. Rapid development of immune checkpoint inhibitors for lung cancer: We haven’t seen a PD-1 or PD-L1 inhibitor approved by the FDA for lung cancer yet, but immunotherapies have only continued to gain momentum and street cred as multiple new agents show comparable activity in a subset of patients. Though it’s not most patients, the ones who respond often respond very well and for a very long time. Multiple companies are tripping over themselves trying to study these immune checkpoint inhibitors in every clinical setting and in combination with every other treatment for lung cancer. These agents are approaching escape velocity for lung cancer.
2. We broke the impasse against acquired resistance for both ALK and EGFR mutation-positive patients: The FDA approved Zykadia (ceritinib) for XALKORI-refractory ALK-positive NSCLC, and the evidence shows it is even more active for XALKORI-naïve patients. It also has clear activity against brain metastases, an Achilles heel for XALKORI over the past several years. Now with multiple generally well-tolerated and very active additional second generation ALK inhibitors moving through clinical testing, we are at the cusp of having an enviable choice of options and potentially soon being able to select particular agents for particular ALK mutations.
Though we don’t yet have a new agent for acquired resistance in EGFR mutation-positive disease commercially available, both AZD9291 and rociletinib (CO-1686) broke out as among the biggest stories at ASCO 2014. The trials with these agents are rolling out worldwide, and we should hope and expect to see one of these become commercially available in the not too distant future.
3. Genomic testing goes mainstream: Though broad “multiplex” testing of a multitude of genes in one panel hasn’t yet delivered on its great promise, since there aren’t yet enough “actionable” mutations to help most patients, this testing, as offered by Foundation Medicine, Caris, and many other large labs is rolling out everywhere. I see this as a big investment in the short term and long term future for cancer treatment. Without knowing exactly where it will lead us, the availability of broad multiplex molecular testing and “next generation sequencing” platforms make most people treating cancer feel that we’re entering a new era of both understanding and treatments matched to the cancer. It will also lead to a new classification of cancer based more on the mutation(s) seen in the cancer than the anatomic definition of a cancer based on its tissue of origin.
4. Modest gains for big populations with advanced non-small cell lung cancer: The median survival benefit seen with the addition of Cyramza (ramucirumab), an antiangiogenic antibody administered every 3 weeks, to Taxotere (docetaxel) on the REVEL trial can’t be considered revolutionary, seeing any treatment move the needle for previously treated patients is a welcome change. This is especially true when this approach includes the oft-excluded patients with squamous NSCLC. The study was enough to lead to the approval of Cyramza in lung cancer by the FDA just in the last few weeks. This year also saw the approval in the EU of Vargatef (nintedinib), an oral anticancer therapy that also blocks angiogenesis, in combination with Taxotere for patients with advanced lung adenocarcinoma, based on an approximately 2 month improvement in median survival with the combination of Vargatef with Taxotere on the large phase III LUME Lung-1 trial.
5. CMS approves low dose chest CT (LDCT)screening for high-risk Medicare patients, with stipulations. After a year of active debate and campaigning over the cost and anticipated benefits vs. risk of widespread screening of higher risk patients (age 55-74, 30 “pack-year” or greater smoking history, current smoker or quit in last 15 years), the Center for Medicare and Medicaid Services (CMS) finally voted to approve LDCT screening for the specific population studied in the large NLST study that demonstrated a significant survival benefit. This approval was accompanied by unprecedented restrictions that included a strict mandate about patients conforming to the age and tobacco exposure requirements specified, including detailed counseling about the high potential for ambiguous lung nodules and the need for smoking cessation counseling, and a restriction of approved LDCT screening to the centers that had developed experience with it in earlier screening trials.
There has been significant debate about whether these limitations will do more to enforce best practices and high quality screening or serve as a barrier for appropriate candidates to pursue screening. This debate also includes questions of the true intent of the seemingly lofty goals, which should help to also limit costs for coverage. But seeing validation of the concept of LDCT screening for appropriate patients after so much skepticism represents a victory for the lung cancer community that will definitely lead to a reduction in deaths from lung cancer and a shift to far more patients being treated at an earlier stage of disease.
Please join us for this important last #LCSM chat on Thursday – we’d love to learn your perspective about these topics and others that you think should be considered as major highlights in lung cancer in 2014. And after a break on New Year’s Day, we’ll pick up again on January 15th with a chat that focuses on predictions and a wish list in lung cancer for 2015.
Check it out Thursday, December 18th, 8 PM ET/5 PM PT at http://www.tchat.io/rooms/lcsm or filter by #LCSM on twitter and add it to your tweets during that hour. Hope to see you then!