Clinical Brief – October 9th
ESMO, or the European Society of Medical Oncology Congress, is an annual gathering of cancer experts and patient advocates. This is the last bit of my notes on some of the studies presented at this year’s ESMO that may be of use.
Adding a targeted therapy to endocrine therapy for HR+ breast cancer can increase the risk of side effects. But some targeted therapies may pose greater risks than others.
Researchers from the Institut Jules Bordet, Belgium, led a meta-analysis of trials to profile the comparative risks between classes of add-on targeted therapies.
In 15 trials involving nearly 8k patients, they found that the odds of a moderate or severe (Grade 3-4) side effect were highest with CDK4/6 inhibitors, followed by anti-HER2 agents, PI3K inhibitors, and mTOR inhibitors. Drugs belonging to these respective classes are listed below. It’s not clear which drugs were included in their analysis.
The odds of experiencing a side effect with targeted + endocrine therapies vs endocrine therapy alone was
2.95-times higher for CDK4/6 inhibitors
2.33-times higher for anti-HER2 agents
2.05-times higher for PI3K inhibitors
1.98-times higher for mTOR inhibitors
The types of side effects were also different between classes. The risk of moderate or severe fatigue was significantly higher with anti-HER2 agents, CDK4/6 inhibitors, and PI3K inhibitors, but not mTOR inhibitors.
The risk of moderate or severe diarrhea was significantly higher with anti-HER2 agents, PI3K inhibitors, and mTOR inhibitors, but not CDK4/6 inhibitors.
Data such as these should help when considering adding a targeted therapy to endocrine therapy.
CDK4/6 inhibitors include abemaciclib (Verzenio), palbociclib (Ibrance), and ribociclib (Kisqali). Anti-HER2 agents include lapatinib (Tykerb/Tyverb), pertuzumab (Perjeta), trastuzumab (Herceptin), ado-trastuzumab emtansine (Kadcyla, also known as T-DM1). PI3K inhibitors: none approved for breast cancer. mTOR inhibitors: everolimus (Afinitor).
Women receiving weekly chemo for metastatic breast cancer may be at risk of pneumonia caused by the Pneumocystis jiroveci fungus.
Researchers from the Addenbrooke’s Hospital, UK, screened nearly 50 patient records in their own system. Everyone was on weekly epirubicin/paclitaxel chemotherapy.
After an average of 21 weeks of chemo, 16% of women had reduced lymphocyte counts, which indicated a compromised immune system.
Upwards of 1 in 10 women with metastatic breast cancer on weekly epirubicin/paclitaxel came down with confirmed or probable pneumonia caused by the Pneumocystis jiroveci fungus.
These stats need to be confirmed through larger cohorts involving multiple hospitals. But for patients who are scheduled to get this chemo treatment, here are some symptoms of Pneumocystis jiroveci pneumonia to watch out for.
T-DM1 (Kadcyla) is said to be a standard second-line treatment for HER2+ metastatic breast cancer. But its efficacy may vary depending on how positive the tumors are for HER2.
Researchers from St. Luke’s International Hospital, Japan, looked through the records of 36 women who were treated with T-DM1 for HER2+ metastatic breast cancer.
About 80% of women had high HER2 expression and were classed as IHC3+; 21% had a weaker HER2 expression and were classed as IHC2+/ISH+.
Among women with high HER2 expression, the tumor response rate was 53% and median progression-free survival was 7 months.
Compare this against results in women with weaker HER2 expression, whose tumor response rate was 0% and median progression-free survival was 2 months.
Granted that this is data from a very small patient set in a single hospital, so again, larger cohorts are needed to confirm their findings.
For context, the NCCN recommends anti-HER2 therapy for patients who are IHC3+ or ISH+.
Palbociclib (Ibrance) is a relatively new treatment for women with HR+ HER2- metastatic breast cancer. Studies have used it in combination with fulvestrant or letrozole. The efficacy of these combinations, in terms of progression-free survival, may not be better than everolimus (Afinitor) + exemestane, an older combination treatment.
Researchers from the City Hospital in Rimini, Italy, did a network meta-analysis of studies involving the two drugs. For palbociclib, they pulled data from the PALOMA 2 and 3 trials. For everolimus, they pulled data from the BOLERO 2 trial and the Bachelot et al network meta-analysis.
Looking at the pooled hazard ratios, they failed to find any significant difference between everolimus + exemestane and palbociclib + fulvestrant or palbociclib + letrozole.
“It follows that [data on] the safety or the economic profile could help physicians in daily clinical practice.”
– Cherubini C, et al.
…in lieu of a head to head trial, that is.
Clinical benefit of palbociclib (Ibrance) + fulvestrant may be dampened as a result of prior therapies used to treat HR+ metastatic breast cancer.
Researchers from France reviewed data from 60 patients treated with palbociclib + fulvestrant as part of the French Temporary Authorization for Use program at the Institut de Cancérologie de l’Ouest. Patients were followed-up for a median of about 8 months.
On average, palbociclib + fulvestrant was the 6th line of treatment for their patients. Prior treatments included hormonal therapy and chemotherapy. All patients had previously taken everolimus.
The median progression-free survival was about 6 months. Median overall survival was not reached. Previous treatment with fulvestrant did not appear to affect progression-free survival with palbociclib + fulvestrant.
The most common side effects were low neutrophil counts, low platelet counts, and anemia.
The reported progression-free survival in this cohort was about 6 months, which is notably shorter than the reported 9 months in the PALOMA 3 trial.
I’m committing another statistical sin here by comparing between unrelated patient populations. Still, patients in PALOMA 3 relapsed on endocrine therapy too, so it’s not entirely a random trial to compare against.
Hopefully, as hospitals learn more about their own experiences, we’ll get to see larger cohorts of real-world data come out at next year’s ESMO.
If you’ve been following my notes over the last little while, I hope you found something useful.
As I get back on Twitter after my little “off-line break”, be sure to drop by and say hi 🤓.