Adjuvant Chemo Might Prevent 7,000 NSCLC Deaths Worldwide Each Year

November 1, 2003

This special “annual highlights” supplement to Oncology News International is acompilation of major advances in the management of lung cancer during 2003, asreported in ONI. Guest editor Dr. Roy Herbst comments on the reports includedherein and discusses advances in the clinical management of lung cancer, with afocus on developments in targeted therapy, new combinations, adjuvant therapy,induction therapy, and what to watch for in 2004.

CHICAGO-Adjuvantcisplatin (Platinol)-based chemotherapysignificantly improved survival inpatients with completely resectednon-small-cell lung cancer (NSCLC),Thierry Le Chevalier, MD, reported atthe plenary session of the 39th AnnualMeeting of the American Society ofClinical Oncology (abstract 6). Dr. LeChevalier, professor of medicine,Institut Gustav-Roussy, Villejuif,France, concluded that adjuvant chemotherapycould be recommendedand might prevent 7,000 deaths worldwidefrom NSCLC every year.The International Adjuvant LungCancer Trial (IALT), which included1,867 patients treated in 148 centersin 33 countries across five continents,showed that chemotherapy conferreda 4.1% absolute benefit in overall survivaland a 5.1% absolute benefit indisease-free survival after 5 years.IALT was designed to confirm resultsfrom the 1995 NSCLC overviewmeta-analysis, which suggestedcisplatin-based adjuvant chemotherapymight increase the 5-year surviv-al rate by 5% after resection, Dr.Le Chevalier said. The IALT study randomized932 patients to adjuvant chemotherapyand 935 patients to placebofollowing surgery for NSCLC.Patients in the study reflected thetypical patient population withNSCLC: 80% were male with a medianage of 59 years; 47% had squamouscell carcinoma, 40% had adenocarcinoma,and the rest had other types oflung cancer.Although chemotherapy differedacross treatment settings, all sites deliveredcisplatin up to a total of 300 to400 mg/m2 in three or four cycles, with74% providing at least 240 mg/m2 ofcisplatin. The drug combined withcisplatin varied by treatment sites-56% used etoposide, 27% usedvinorelbine (Navelbine), 11% usedvinblastine, and 6% used vindesine.Some centers provided thoracic radiotherapyat a dose of 60 Gy based onthe N stage of disease. Before enteringthe study, most patients in the studyhad undergone lobectomy (64%); 35%had pneumonectomy, and 1% segmentectomy.More than 98% of patients enrolledin the study were still alive for followupin 2000. The median follow-up forthe entire patient sample at the timeof data analysis in September 2002 was56 months.Overall survival was statistically significantbetween the two arms of thestudy. Median survival was 50.8months in the chemotherapy-treatedgroup and 44.4 months in the placebogroup. The median disease-free survivalwas 40.2 months among patientstreated with chemotherapy vs 30.5months among those given a placebo.The 5-year overall survival rate, theprincipal objective of the study, was44.5% in the chemotherapy arm and40.4% in the control arm (hazard ratio,0.86; P < .03). The 5-year disease-freesurvival was 39.4% in the chemotherapygroup and 34.3% in the placebo group(hazard ratio, 0.83; P < .003).In the chemotherapy arm, 23% ofpatients experienced at least one grade4 toxicity, primarily neutropenia(18%), and 7 patients (0.8%) had lethaltoxicity.'Data Compelling'Data from the trial were compelling,and the study was sufficientlystrong enough to provide a qualified"yes" to the question, should cliniciansuse adjuvant chemotherapy afterresection, said discussant DavidJohnson, MD, director of the divisionof medical oncology, department ofmedicine, Vanderbilt University MedicalCenter. "There is mounting evidencethat postoperative chemotherapybenefits some patients withNSCLC," he said.Dr. Johnson pointed out that questionsnevertheless remain about howto select appropriate candidates forpostoperative chemotherapy and whatregimen to employ. He recommendedusing clinical parameters for patientselection, such as performancestatus, speed of postoperative recovery,number of comorbid conditions,and perhaps pathologic stage or gene profiling. It seems clear, he added, thatthe chemotherapeutic regimen shouldbe platinum-based.Adjuvant chemotherapy after resectionfor NSCLC is "out of the gate,and the race is on to build on theprovocative results from this trial," Dr.Johnson said.