“Although checkpoint blockade immunotherapies have advanced rapidly in the treatment paradigm for patients with non–small cell lung cancer (NSCLC), interest in developing targeted therapies for this malignancy has remained high. Building on the success of molecularly targeted drugs aimed at relatively small subsets of patients, researchers are increasingly aiming at the MET oncogene.
“During the past several years, interest in MET activity has grown as investigators have considered it both as a biomarker and target for treatment, particularly since the focus on MET exon 14 skipping mutations has led to the development of several second-generation MET inhibitors, according to Balazs Halmos, MD, MS.”
“Recently reported updates from the KEYNOTE-189 and IMpower150 trials demonstrated the powerful impact of adding immunotherapy to treatment regimens for patients with non–small cell lung cancer (NSCLC).
“In the phase III KEYNOTE-189 study, the combination of pembrolizumab (Keytruda) with chemotherapy in the frontline setting improved survival in patients with nonsquamous NSCLC. In this trial, which is the confirmatory trial for the FDA approval of pembrolizumab plus carboplatin/pemetrexed, patients received frontline pembrolizumab or placebo combined with pemetrexed and either cisplatin or carboplatin. The study met the primary endpoints of improved overall survival (OS) and progression-free survival (PFS), though full data have yet to be presented.”
“Circulating tumor DNA (ctDNA) can help differentiate what is known as pseudoprogression from true progression of disease in patients with melanoma who are treated with programmed death 1 (PD-1) inhibitors, according to a new study. It also showed that ctDNA could be used as a powerful biomarker to predict long-term outcomes.
” ‘Pseudoprogression, a response that occurs after the initial development of new lesions or an increase in the size of target lesions, occurs in up to 10% of patients treated with PD-1 antibodies,’ wrote study authors led by Jenny H. Lee, MBBS, of Macquarie University in Sydney, Australia. ‘Confirmation of pseudoprogression requires subsequent imaging, imposing an ongoing challenge.’ ”
“The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) improved progression-free survival (PFS) compared with chemotherapy in treatment-naïve patients with high tumor mutation burden (TMB) non–small cell lung cancer (NSCLC).
“Bristol-Myers Squibb (BMS), the manufacturer of both immunotherapies, announced the preliminary findings from part 1a of the phase III CheckMate-227 trial in a press release. The company did not report any further data.”
“Some patients with unresectable or metastatic melanoma who receive immunotherapy and continue therapy after progression have decreased tumor burden, and survival is improved when the therapy is continued as well, according to a new pooled analysis.
“Since the approval of immune therapies for melanoma, concerns have been raised regarding the adequacy of standard RECIST criteria to identify responses and progression. ‘Patients who receive immunotherapy might develop an atypical response pattern, wherein they initially meet conventional response criteria for progressive disease but later have decreases in tumor burden,’ wrote study authors led by Julia A. Beaver, MD, of the US Food and Drug Administration in Silver Spring, Maryland.”
“Beta blockers appear to affect immune cells and improve immune function, and now investigators are reporting that beta blockers may play an important role in boosting immunotherapy in patients with metastatic melanoma. Researchers at Penn State University conducted a retrospective study and found that melanoma patients who received immunotherapy while taking a pan beta blocker lived longer than patients who received immunotherapy alone.”
“Although modern immunotherapy has yet to have a breakthrough in prostate cancer to the degree it has had in lung cancer or urothelial carcinoma, combinations with anti–PD-1/PD-L1 agents are beginning to show promise for these patients in clinical trials.
“Currently ongoing is a phase II trial of durvalumab (Imfinzi) in combination with the PARP inhibitor olaparib (Lynparza) in patients with metastatic castration-resistant prostate cancer (mCRPC; NCT02484404). Investigators note that previous data have suggested that 25% to 30% of sporadic mCRPC has DNA-repair pathway defects. Results thus far have demonstrated that the synergy of durvalumab and olaparib proves that the combination may be a viable option for patients with mCRPC who are heavily pretreated. The trial is still accruing.”
“A combination of pembrolizumab (Keytruda) and trastuzumab, tested in patients with trastuzumab-resistant advanced HER2-positive breast cancer, was well tolerated and had clinical benefit in patients whose tumors were positive for a biomarker for pembrolizumab, according to data presented from the phase Ib/II PANACEA trial at the 2017 San Antonio Breast Cancer Symposium, held Dec. 5–9.
“ ‘We wanted to investigate if immunotherapy approaches can work in patients with advanced HER2-positive breast cancer that is resistant to trastuzumab,’ said Sherene Loi, MD, PhD, associate professor at Peter MacCallum Cancer Centre in Melbourne, Australia, working with the International Breast Cancer Study Group (IBCSG).”