Breaking News
March 21, 2018 - Dermira’s Two Phase 3 Trials Evaluating Olumacostat Glasaretil in Patients with Acne Vulgaris Did Not Meet Co-Primary Endpoints
March 21, 2018 - ‘Oh, It Was Nothing’
March 21, 2018 - Herbal drug kratom linked to salmonella illnesses, CDC says
March 21, 2018 - New optical point-of-care device could enhance screening for thyroid nodules
March 21, 2018 - FDA Expands Approval of Adcetris (brentuximab vedotin) for First-Line Treatment of Stage III or IV Classical Hodgkin Lymphoma in Combination with Chemotherapy
March 21, 2018 - Eosinophilic Esophagitis: Late Manifestation of Allergic March
March 21, 2018 - Signaling pathway involving the Golgi apparatus identified in cells with Huntington’s disease
March 21, 2018 - Quintupling inhaled steroid doses may not benefit children with asthma
March 21, 2018 - Study shows clear connection between cardiovascular fitness in middle age and dementia risk
March 21, 2018 - Premature babies have higher risks of health complications in Bangladesh
March 21, 2018 - Child’s temperament and parenting influence weight gain in babies
March 21, 2018 - Researchers find the heart to be capable of arrhythmia termination after local gene therapy
March 21, 2018 - Inhealthcare to provide digital infrastructure for NHS to help protect people from falls
March 21, 2018 - Flu Season Finally Slowing Down
March 21, 2018 - Mixed Results for Shorter DAPT in ACS Patients
March 21, 2018 - Scientists discover fish scale-derived collagen effective for healing wounds
March 21, 2018 - Genomics England announces new partnership to improve efficiency of next-generation sequencing analysis
March 21, 2018 - Adjuvant AC chemotherapy found to be effective in treating HRD-positive breast cancer patients
March 21, 2018 - Researchers identify new treatment targets for lung diseases using big data
March 21, 2018 - Kids see more women in science than five decades ago
March 21, 2018 - Research shows link between chronic fatigue syndrome and lower thyroid hormone levels
March 21, 2018 - Alzheimer’s disease on the rise
March 21, 2018 - Two Agents Equal as Pretreatment for Adrenal Tumor Surgery
March 21, 2018 - ‘Icebreaker’ protein opens genome for T cell development, researchers find
March 21, 2018 - Women in medicine shout #Metoo about sexual harassment at work
March 21, 2018 - Mother’s pre-pregnancy waist size may be linked to child’s autism risk
March 21, 2018 - Second hand marijuana smoke can cause serious damage
March 21, 2018 - International study shows benefits of using MRI at the start of prostate cancer diagnosis
March 20, 2018 - Santhera Reports Outcome of Exploratory Trial with Idebenone in PPMS Conducted at the NIH
March 20, 2018 - ECG Patch Ups At-Home Afib Diagnosis in mSToPS Trial
March 20, 2018 - ROS-scavenging nanozymes for anti-inflammation therapeutics
March 20, 2018 - Genomics England announces appointment of global genomics pioneer as first CEO
March 20, 2018 - Test flight at German Aerospace Center in Cologne demonstrates functionality of deficopter
March 20, 2018 - Music therapy helps treat combat-related psychological injuries in military personnel
March 20, 2018 - Innovative psychotherapeutic treatment protocol for obsessive-compulsive disorders
March 20, 2018 - Weight loss after lap-band surgery alleviates arthritic knee pain
March 20, 2018 - New diabetes drug may help obese people shed body weight
March 20, 2018 - Novel Peanut OIT a Winner in Phase III Trial
March 20, 2018 - Can gene therapy be harnessed to fight the AIDS virus?
March 20, 2018 - Education and academic achievement can lessen effects of child abuse, neglect
March 20, 2018 - Researchers develop new algorithm to make CPR more effective
March 20, 2018 - Diabetes medication reduces chance of late miscarriage, premature birth among women with PCOS
March 20, 2018 - SSRIs may be more effective option for treating anxious youth, UC research shows
March 20, 2018 - Antibiotics could benefit women suffering from chronic bladder pain
March 20, 2018 - Health Highlights: March 16, 2018
March 20, 2018 - Interventional Radiology Has a Problem of ‘Unseen’ Value
March 20, 2018 - Antibodies show effectiveness for HIV prevention and promise for treatment and cure
March 20, 2018 - New 3-D-printed technology will improve radiology training
March 20, 2018 - New study identifies key role for particular gene in 16p11.2 deletion syndrome
March 20, 2018 - Red and processed meat increase the risk of liver disease
March 20, 2018 - 50% of Australians do not brush teeth twice a day
March 20, 2018 - American Gene Technologies receives second immuno-oncology patent
March 20, 2018 - Study finds no link between long-term violent video game play and adult aggression
March 20, 2018 - Weight loss surgery widely underutilized among young patients with severe obesity
March 20, 2018 - Scientists uncover new answers to cell aging in children with rare, fatal disease
March 20, 2018 - The Pistoia Alliance Calls for Greater Life Sciences Collaboration to Build the ‘Lab of the Future’
March 20, 2018 - Morning Break: Psychopathic Thought; Americans Flout Zzz’s; Farm to Pharma
March 20, 2018 - Perceptions of old age change as we age
March 20, 2018 - New standards for public involvement in research launched across the UK
March 20, 2018 - Whole Genome Sequencing used as diagnostic solution for TB
March 20, 2018 - Researchers show how two cancer genes work together to trigger leukemia
March 20, 2018 - Scientists discover basic molecular mechanism that helps understand how ALS works
March 20, 2018 - Multi-center study to evaluate promising new intervention for upper limb dysfunction after SCI
March 20, 2018 - Researchers develop technology to program DNA for delivering cancer drugs
March 20, 2018 - Northwestern scientists bring precision medicine to rheumatoid arthritis
March 20, 2018 - Research suggests possible link between heading a soccer ball and brain imbalance
March 20, 2018 - Robocall increases diabetic retinopathy screening rates among poor minorities
March 20, 2018 - INSYS Therapeutics Initiates Phase 3 Clinical Trial of Cannabidiol (CBD) Oral Solution for Treatment of Infantile Spasms
March 20, 2018 - Little Talk Between Docs and Patients Pre-PSA Screen
March 20, 2018 - Women GPs bring remote care to rural Pakistan
March 20, 2018 - Adults skipping vaccines may miss out on effective new shingles shot
March 20, 2018 - Suppressing emotions appears to reduce negative memories
March 20, 2018 - Epidural stimulation can safely, effectively normalize blood pressure in patients with SCI
March 20, 2018 - ‘Fast track’ project shows promising results in cancer whole genome analyses
March 20, 2018 - Advanced insulin pump system can also manage type 1 diabetes in children, study shows
March 20, 2018 - Flu risk less on flights if in a window seat finds study
March 20, 2018 - Sarepta Therapeutics Announces Plan to Submit a New Drug Application (NDA) for Accelerated Approval of Golodirsen (SRP-4053) in Patients with Duchenne Muscular Dystrophy (DMD) Amenable to Skipping Exon 53
March 20, 2018 - Post-Transplant Fatty Liver Disease on the Rise
March 20, 2018 - New mutation linked to ovarian cancer can be passed down through dad
March 20, 2018 - Alex’s experiences of living with rare genetic disease
Survival Bump in Bladder Cancer with Keytruda

Survival Bump in Bladder Cancer with Keytruda

image_pdfDownload PDFimage_print

Action Points

  • Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

SAN FRANCISCO — Patients with recurrent urothelial cancer lived longer when they received pembrolizumab (Keytruda) instead of chemotherapy as second-line treatment, according to long-term follow of a randomized trial.

After a median follow-up of 28 months, patients treated with pembrolizumab had a median survival of 10.3 months versus 7.3 months for those who received chemotherapy. Both 12- and 24-month survival was significantly better in the group treated with the immunotherapeutic drug, according to Joaquim Bellmunt, MD, of Dana-Farber Cancer Institute in Boston, and colleagues.

PD-L1 expression status did not influence response to treatment with pembrolizumab or the survival benefit, they reported here at the Genitourinary Cancers Symposium.

“Pembrolizumab is the first immunotherapy to demonstrate superior survival over chemotherapy in patients with advanced urothelial carcinoma after failure of platinum-based therapy,” Bellmunt said. “This study provides level 1 evidence that supports the use of pembrolizumab as a standard of care for this patient population.”

Data from the trial, known as KEYNOTE 045, provided the basis for approval of pembrolizumab for advanced urothelial carcinoma, irrespective of PD-L1 status, in the U.S., Europe, and Japan, he added. The 2-year follow-up data remained consistent with the data that supported the approval.

A different PD-1/PD-L1 inhibitor failed to demonstrate an advantage over chemotherapy for PD-L1-positive locally advanced/metastatic urothelial cancer that progressed or relapsed after initial platinum-based chemotherapy. As previously reported, patients treated with atezolizumab (Tecentriq) had a median overall survival (OS) of 11.1 months versus 10.6 months for investigator’s choice of chemotherapy. An intention-to-treat (ITT) analysis of all treated patients, irrespective of PD-L1 status, yielded a similar result, reported Thomas Powles, MD, of Barts Cancer Institute in London.

The pembrolizumab results should increase confidence in second-line use of the drug, said invited discussant Robert Jones, MD, PhD, of the University of Glasgow in Scotland.

“This helps our patients make an informed decision about whether or not to accept this treatment,” said Jones. “The results remain in keeping with the possibility of a long immunotherapy [survival] tail. None of these data support a role for second-line cytotoxics after failure of platinum in preference to a checkpoint inhibitor.”

The pembrolizumab data affirmed findings initially reported at the 2016 Society for Immunotherapy of Cancer, followed by publication in the New England Journal of Medicine. At that point, after a median follow-up of 14 months, the median OS was 10.3 versus 7.4 months for the pembrolizumab and chemotherapy arms, respectively.

KEYNOTE 045 involved 542 patients whose disease had progressed or relapsed after first-line platinum-based chemotherapy. Almost half the patients had two or more high-risk characteristics.

The patients were randomized to pembrolizumab or the investigators’ choice of three different chemotherapy options: paclitaxel, docetaxel, or vinflunine. The trial had coprimary endpoints of OS and progression-free survival (PFS), as assessed in the ITT population and according to PD-L1 status (using ≥10% PD-L1 expression in tumor cells, lymphocytes, and macrophages to define positivity).

The initial results in favor of pembrolizumab represented a 27% reduction in the survival hazard (P=0.0022). The updated data reflected a 30% reduction in the survival hazard (95% CI 0.57-0.85, P=0.00017). The 12-month survival was 44.4% with pembrolizumab and 29.8% with chemotherapy, and the 24-month survival was 27.0% versus 14.3% with pembrolizumab and chemotherapy, respectively.

“By 24 months, 60% of patients in the chemotherapy arm had received an immunotherapeutic agent, including those who received pembrolizumab at crossover,” said Bellmunt.

Subgroup analysis demonstrated a consistent survival advantage for patients treated with pembrolizumab.

Analysis by PD-L1 status showed a median OS of 8.0 months with pembrolizumab and 4.9 months with chemotherapy in the PD-L1-positive patients (n=124) and 10.8 versus 7.7 months in the PD-L1-negative group.

Median PFS did not differ significantly between treatment groups after 14 or 28 months of follow-up (2.1 vs 3.3 months) although the proportion of patients who remained progression free at 12 months (18.4% vs 9.5%) and 24 months (12.5% vs 2.5%) favored pembrolizumab.

Objective response rate was twice as high with the PD-1 inhibitor than with chemotherapy (21.1% vs 11.0%).

Pembrolizumab was associated with a more favorable adverse-event profile, as patients treated with chemotherapy had more fatigue, diarrhea, asthenia, anemia, constipation peripheral sensory neuropathy, peripheral neuropathy, decreased neutrophil count, neutropenia, and alopecia. Immune-related adverse events occurred more often with pembrolizumab: hypothyroidism, pneumonitis, hyperthyroidism, and colitis.

Investigators in the atezolizumab study, known as IMvigor211, performed extensive exploratory analyses to gain insight into the negative result. They found a correlation between DNA damage response (DDR) mutations tumor mutational burden (TMB). Additional analysis showed no association between DDR and efficacy. However, they identified a significant benefit of atezolizumab in the small subgroup of patients (about 100 of 931) who had high TMB and tested positive for PD-L1 expression (IC 2/3): median OS of 17.8 versus 10.6 months, representing a 50% reduction in the hazard ratio (95% CI 0.29-0.86).

In his review of the two trials, Jones concluded that neither provided compelling evidence of a biomarker to predict response to PD-1/PD-L1 inhibition.

The KEYNOTE 045 trial was supported by Merck.

Bellmunt disclosed relevant relationships with Astellas, AstraZeneca/Medimmune, Bristol-Myers Squibb (BMS), Genentech, Merck, Novartis, Pfizer, Pierre Fabre, Millennium, and Sanofi.

The study by Powles’ group was supported by Roche/Genentech.

Powles disclosed relevant relationships with BMS, Merck, Roche/Genentech, AstraZeneca, MedImmune, Novartis, and Ipsen.


Tagged with:

About author

Related Articles