Adjuvant Treatment Yields Survival Benefit in Early-Stage NSCLC

NEW ORLEANS -Two phaseIII studies have shown that adjuvantchemotherapy after resection significantlyimproves survival for patientswith early-stage non-small-cell lung cancer (NSCLC), compared with surgeryalone. Previous randomized trialsof cisplatin (Platinol)-based adjuvantchemotherapy in stages IA to IIINSCLC have shown no survival benefit(Adjuvant Lung Project Italy,ALPI) or modest but significant benefit(International Adjuvant LungTrial, IALT). The new results, fromUS and Canadian studies that enrolled only early-stage patients, were presentedas late-breaking abstracts at the40th Annual Meeting of the AmericanSociety of Clinical Oncology.CALGB 9633Gary M. Strauss, MD, MPH, ofBrown University and Rhode IslandHospital, reported that adjuvantcarboplatin (Paraplatin) plus paclitaxelprovided a 4-year overall survivalbenefit of 12%, compared withobservation (abstract 7019) in patientswith stage IB NSCLC. This is the firstrandomized trial to evaluate thiscombination in the adjuvant settingin early-stage lung cancer.In this study, CALGB 9633, whichwas sponsored by CALGB, RTOG,and NCCTG, 344 patients with stageIB NSCLC (tumors at least 3 cm indiameter) who had undergone completesurgical resection of the tumorwere randomized to receive paclitaxel 200 mg/m² over 3 hours andcarboplatin AUC 6, each administeredon day 1 every 3 weeks for four cycles,or to no further treatment. Medianfollow-up is 34 months. He noted thatthe mean tumor diameter was 4.6 cm.Overall survival at 4 years was 71%with chemotherapy vs 59% with observation.Death from any cause occurredin 38 treatment patients (21%)vs 52 controls (30%) (HR = 0.62,P = .028). This 38% proportional reductionin all-cause mortality withadjuvant chemotherapy translatesinto a 12% absolute improvement,Dr. Strauss said.Overall survival at 4 years was 71%with chemotherapy vs 59% with observation.Death from any cause occurredin 38 treatment patients (21%)vs 52 controls (30%) (HR = 0.62,P = .028). This 38% proportional reductionin all-cause mortality withadjuvant chemotherapy translatesinto a 12% absolute improvement,Dr. Strauss said.At 4 years, the risk of dying fromlung cancer was 15% for patients whoreceived chemotherapy vs 26% forcontrols. Overall, there have been 19lung cancer deaths (11% mortality)with chemotherapy and 34 (20%)with observation (HR = 0.51, P =.018). This 49% proportional reductionin lung cancer mortality translatesinto an 11% absolute improvementwith use of chemotherapy.Adjuvant chemotherapy was welltolerated, with no chemotherapy-relatedtoxic deaths. Grade 3-4 neutropeniaoccurred in 36% of patients."Our study demonstrates unequivocalefficacy for adjuvant chemotherapyin early lung cancer," Dr. Straussconcluded.JBR.10In the Canadian study, 482 patientswith completely resected stage I or IINSCLC were randomized to adjuvantvinorelbine (Navelbine)/cisplatin orobservation. Five-year survival was69% in the treated group vs 54% for observation (HR = 0.7, P = .012), fora 30% reduction in death and anabsolute survival benefit of 15%(P = .0022), reported Timothy L.Winton, MD, on behalf of the NationalCancer Institute of CanadaClinical Trials Group (NCIC-CTG)(abstract 7018). Dr. Winton is withthe University of Alberta and the CapitalHealth-affiliated University ofAlberta Hospital.In this study, JBR.10, patients receivedcisplatin 50 mg/m² on days 1and 8 every 4 weeks for four cyclesplus vinorelbine 25 mg/m² weekly for16 weeks. The original protocol, whichcalled for 30 mg/m²/wk of vinorelbine,was modified in August 1995 becauseof hematologic toxicity and patientcompliance issues.Median survival in the adjuvant chemotherapy patients was 94 months vs73 months for observation (HR = 0.69,P = .011). The average time to recurrencewas 46.7 months for observationand has not been reached in thetreatment arm. Dr. Winton reportedthat the combination was well tolerated.Impact on quality of life was limited,except for neurotoxicity.Discussant Katherine M.W.Pisters, MD, of M.D. Anderson, saidthat the two studies "confirm the positiveIALT findings of a benefit forpostoperative plantinum-based chemotherapyin completely resectedNSCLC." She called adjuvant platinum-based chemotherapy in NSCLCa new standard of care that "shouldbe recommended to completelyresected NSCLC patients with goodperformance status."