Dec 14, 2018

Mix and match

The story

As much as you can empathize with trouble waking up, it’s a real problem for the immune system in advanced cancer. Here's how adding chemo to immunotherapy boosts outcomes in triple negative breast cancer (TNBC).

The sleeping giant

Immunotherapy responses tend to be durable, but only when they happen. That's why triggering the immune system in traditionally unresponsive cancers is among the field's key challenges. Adding chemotherapy to immunotherapy is thought to boost the immune response by increasing tumor antigen release, but to date the strategy has been validated only in immunogenic cancers like non-small cell lung. PD-1 inhibitors, the backbone of immunotherapy in lung cancer, have never shown broad efficacy in breast cancer.

The trial

Patients with TNBC – roughly 14% of new breast cancer diagnoses – face poor clinical outcomes, and chemotherapy remains the standard first-line treatment for advanced disease. IMpassion130 evaluated chemo agent nab-paclitaxel with or without PD-L1 inhibitor atezolizumab in 450 TNBC patients. The immunotherapy group saw marginally improved progression-free survival (7.2 vs. 5.5 months), though an overall survival (OS) difference was not significant. In the 40% of patients whose tumors expressed PD-L1, median OS was 25 months for combined therapy vs. 15 months with chemo alone.

The takeaway

PD-L1 positive patients saw a strong benefit from combination chemo-immunotherapy in TNBC, a disease that has not seen a breakthrough in years. Be on the lookout for more efforts to engineer immunotherapy to work in new settings.

Say it on rounds

When you get a page that your co-residents definitely need to see

'Show, don't tell' is a good rule of thumb for a residency email blast, but does it work for patient adherence? VIPVIZA explored whether picture evidence of disease could help sway patients to comply with medical advice in 3,500 adults with elevated cardiovascular risk. Patients either received a picture of their own carotid doppler results (see example) plus a phone call from a nurse or usual care. At 1 year, patients in the education group had improved Framingham Risk Scores and lower LDL cholesterol than their peers. Follow up studies will track actual cardiac events.

When rounds are on pace to drag past lunch

Time for early intervention. Cancer patients are at high risk for venous thromboembolism (VTE), but outpatient prophylaxis with heparin agents hasn't shown clear benefit. AVERT randomized 550 cancer patients with elevated VTE risk (Khorana score ≥2) to low-dose apixaban or placebo at the start of chemotherapy. At 6 months, apixaban cut the rate of VTE in half (4% vs. 10% with placebo) due to a decrease in pulmonary embolism in the treatment group. Apixaban patients had a slight increase in bleeding events.

When it takes you twice as long to write notes from home

At least you have the option. Cognitive behavioral therapy (CBT) is an effective treatment for irritable bowel syndrome (IBS), though it has yet to gain broad acceptance due to time intensity and stigma. A RCT of 440 patients with treatment-refractory IBS found that 4 sessions of home-based CBT were as effective as a 10-session clinic-based model. At 1-year follow-up, about 40% of patients in the home CBT group maintained improvement in IBS symptoms compared to 20% of patients in an education-only group.
Am J Gastroenterol

Brush up

C. diff infection

Unlike other hospital-acquired infections, C. diff is on the rise. The bug is thought to cause about 450,000 infections and 30,000 deaths every year. Older patients with recent antibiotic use are at highest risk, and nurses will tell you they can recognize the odor of C. diff diarrhea. Stool PCR is the gold standard for diagnosis, and oral vancomycin, formerly used for refractory or severe disease, is now an initial treatment option for all patients per IDSA guidelines.

What's the evidence

For fecal microbiota transplant (FMT) in C. diff infection? A landmark 2013 study established the practice after 13 of 16 patients who received FMT had resolution of C. diff diarrhea compared to 4 of 13 patients who received PO vanc. Economic analyses suggest the procedure is cost effective, and European consensus guidelines have outlined how to prepare frozen and fresh material for FMT. Whether FMT can help with severe acute colitis or initial infection is less clear, and further research is ongoing.

What your research friends are talking about

Private research funds have seen increased scrutiny since the NIH halted a study on moderate drinking funded by the alcohol industry. Now the agency will formally evaluate all privately funded research for conflicts of interest.

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