Nick Mulcahy

March 22, 2012

March 22, 2012 (Hollywood, Florida) — The guidelines on nonsmall-cell lung cancer (NSCLC) from the National Comprehensive Cancer Network (NCCN) have multiple changes, including an endorsement of video-assisted thoracic surgery (VATS), guidance on the use of the new oral drug crizotinib, and a revised classification for adenocarcinomas.

These changes and others were discussed here at the NCCN 17th Annual Conference.

Thomas D'Amico, MD, from Duke University in Chapel Hill, North Carolina, spoke to the audience about changes in the surgical management of NSCLC.

In stage 1A disease, as part of pretreatment evaluation, the guidelines now read that it "may be preferable" to sample mediastinal lymph nodes with esophageal endoscopic ultrasound/endobronchial ultrasound prior to initiating therapy, reserving mediastinoscopy and mediastinal lymph node dissection until the planned surgical resection.

Mediastinoscopy is a vital tool, noted Dr. D'Amico. He pointed out that 25% of stage I patients are incorrectly staged without mediastinoscopy. "Who wants to be systematically wrong 25% of the time? Nobody."

Dr. D'Amico also championed VATS to meeting attendees. VATS is not only a "reasonable" surgical approach, as the guidelines state, but could be considered "superior," he said. "It's not equivalent, it's better," opined Dr. D'Amico, comparing thoracoscopic lobectomy to thoracotomy or open lobectomy.

VATS is increasingly challenging thoracotomy, he said. In 2007, nearly a third of lung cancer surgeries were minimally invasive thoracoscopy — an increase of 300% from 2002, he noted.

The advantages of thoracoscopic lobectomy include less postoperative pain, faster return to full activity, preservation of pulmonary function, and lower cost (about $2000 per case), Dr. D'Amico explained.

But the "critical outcome advantages," which have been established in the literature, are related to better compliance with adjuvant therapy, fewer complications, and superiority in high-risk patients, he added.

Thoracoscopic lobectomy "should now be considered the standard in early-stage disease," Dr. D'Amico said.

However, the NCCN guidelines are a little less emphatic. A new section of the document says that "in high-volume centers with significant VATS experience, VATS lobectomy in selected patients results in improved early outcomes (pain, hospital length of stay, return to function) without compromise of cancer outcomes."

New Oral Therapy and Molecular Test

Adenocarcinoma in situ is a new classification within adenocarcinomas, a histological subtype of NSCLC. The term refers to nodules that are smaller than 3 cm, have lipidic growth, and are mucinous or nonmucinous. It is "probably the most important change" in the pathology section of the NCCN guidelines, said Richard Cheney, MD, from Roswell Park Cancer Center in Buffalo, New York. This new term will replace [bronchioloalveolar carcinoma], which is now "discouraged," he said.

Dr. Cheney also reminded the NCCN audience that if they are sending out tissue samples for molecular testing for the purpose of deciding upon targeted therapies, then "samples need to be high quality."

For a sample to be high quality, at least 50% to 70% of the tissue must be comprised of cancer cells.

In some cases, a negative test can be explained by testing variables, including poor sample quality, said Dr. Cheney.

In the case of testing for anaplastic lymphoma kinase (ALK) status, which is needed to determine suitability for the newly approved targeted therapy crizotinib (Xalkori, Pfizer), there is a new diagnostic test. This test, which uses fluorescence in situ hybridization, is the "gold standard" and is preferable to immunohistochemistry, which is "controversial" when used for ALK, said Dr. Cheney.

The development of crizotinib is a "remarkable story," said Ramaswamy Govindan, MD, from Siteman Cancer Center and the Washington University in St. Louis, Missouri. The ALK rearrangement mutation was only discovered 4 years ago, he said. "Now we have a drug available at Walgreens," he continued, referring to crizotinib.

Dr. Govindan has patients on the drug "who are alive 3 years later," he said.

Dr. Govindan showed a dramatic graphic depicting the phase 2 study of crizotinib, conducted in 82 patients with NSCLC who were found to have the ALK fusion gene. Almost all of the patients showed some tumor shrinkage.

The US Food and Drug Administration approved crizotinib for the treatment of late-stage NSCLC in August 2011.

Dr. D'Amico has disclosed no relevant financial relationships. Dr. Cheney reports being a consultant for OptumHealth. Dr. Govindan reports being a consultant for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, and Pfizer.

National Comprehensive Cancer Network (NCCN) 17th Annual Conference. Presented March 15, 2012.


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