Bortezomib Warrants Further Study in Advanced Lung Cancer,Two Phase II Trials Suggest

ORLANDO, Florida-Two trialswith bortezomib (Velcade), one inadvanced non-small-cell lung cancer(NSCLC) and the other in small-celllung cancer (SCLC), suggest that ithas some activity in advanced disease.Researchers concluded that it is prematureto test bortezomib in largertrials but that it warrants further study,perhaps in combination with otheragents, in both NSCLC and SCLC.NSCLC Trial vs DocetaxelIn the NSCLC trial, the drug wastested in patients with stage IIIb or IVdisease who had previously receivedone round of chemotherapy (abstract7034). This phase II trial enrolled 158patients and randomized them to eitherbortezomib alone or bortezomibwith docetaxel (Taxotere).Comparable ResponsesResponse rates and survival werecomparable in the two arms. Partialresponses occurred in 8% of patientstaking bortezomib alone and in 9% ofthose taking bortezomib with docetaxel.Some of the outcomes seemedto favor bortezomib in combinationtherapy-median time to progressionwas 1.5 months with bortezomib alonevs 4 months with the bortezomib/docetaxel combination, and more patientshad stable disease on the combinationarm.However, 1-year survival rates weresimilar: 33.1% for bortezomib aloneand 38.7% for the combination. Mediansurvival time was 7.4 months forpatients who received bortezomibalone and 7.8 months for those whoreceived the two drugs combined.Toxicity was low and manageable onboth arms.The results show that activity ofbortezomib is comparable to that ofthe current, standard drugs for second-line therapy of NSCLC, said theinvestigators, who were led by MichaelFanucchi, MD, associate professorof hematology and oncology, WinshipCancer Institute, Emory University,Atlanta. Charles Rudin, MD, PhD,director of the lung cancer therapeuticsprogram at Sidney Kimmel ComprehensiveCancer Center, agreed.'Respectable Results' vsStandard TxThese are "nice results" for bortezomib,he said in his discussion, notingthat the outcomes are "perfectlyrespectable in comparison to any ofthe existing therapies," and adding, "Ithink bortezomib appears to have realactivity in this context-an excitingresult."Although bortezomib is probablynot ready for a large phase III trial, Dr.Lynch said, it would be interesting totest it in a phase II trial with otheragents, particularly with drugs targetedat the epidermal growth factor receptor,or EGFR.SWOG Study in SCLCIn the SCLC study, bortezomibshowed less activity (abstract 7047).Conducted by the Southwest OncologyGroup (SWOG), this phase II trialtested the drug as a single agent inpatients with extensive disease whohad received prior platinum therapy.Patients were stratified according towhether they were sensitive or resistantto platinum therapy.Only 1 of 56 evaluable patients hada partial response and 1 had stabledisease, both in the platinum-resistantgroup. The trial was stopped earlybecause of the poor response rates anda higher-than-expected rate of diseaseprogression.Combination Tx AdvocatedThe investigators, led by Jewel Johl,MD, of the University of California,Davis, Cancer Center, concluded thatthe results do not warrant further studyof bortezomib as a single agent in heavilypretreated SCLC patients. Like theNSCLC researchers, however, Dr. Johland his colleagues think bortezomibcould be active in combination withother agents. They noted that the drug,a proteasome inhibitor, has shown activityin combination with chemotherapyagents that trigger apoptosis inpreclinical and phase I studies.In discussing this study, ThomasLynch, MD, director, Center for ThoracicCancers, Massachusetts GeneralHospital, Boston, agreed that furtherstudy was warranted. "I would arguethat even one response to a single agentin this setting is a proof of principle,"he said, adding that combinations ofbortezomib and other agents shouldbe tested. One such trial, investigatingbortezomib and topotecan (Hycamtin),has already been instituted bySWOG, the investigators said.