Saturday, March 25, 2017

Circulating DNA predicts response to anti-PD1

One more thing I have been yelling about for years!!!  Medicine now has the technology to determine all sorts of things via a simple blood draw. Circulating tiny bits of tumor DNA floating through our blood can tell docs what type of tumor we have, predict response to a given treatment and let us know how the treatment is working.  Here is a link to years of posts:  Circulating DNA in melanoma treatment from 2014 til now!!

Now there's this:

Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma. Lee, Long, Boyd, et al. Ann Oncol. 2017 Jan 24. 

Programmed death 1 (PD1) inhibitors are now a foundation of medical management of metastatic melanoma. This study sought to determine whether circulating tumour DNA (ctDNA) provides useful early response and prognostic information.

We evaluated the relationship between pre-treatment and early on treatment ctDNA and outcome in melanoma patients treated with PD1 inhibitors alone or in combination with ipilimumab.

ctDNA was detected in 40/76 patients (53%) at baseline, and correlated with stage, LDH levels, disease volume and ECOG performance. RECIST response was 72% (26/36) in Group A (undetectable ctDNA at baseline), 77% (17/22) in Group B (elevated ctDNA at baseline but undetectable within 12 weeks of therapy) and 6% (1/18) in Group C (elevated ctDNA at baseline and remained elevated during treatment). The median PFS was not reached in groups A and B and was 2.7 months for Group C. The median OS was not reached for Groups A and B and was 9.2 months for Group C . The poor outcome measures associated with Group C remained significant in multivariate analysis adjusted for LDH, performance status, tumour stage and disease volume. The predictive value for ctDNA for response was confirmed in a separate validation cohort.

Longitudinal assessment of ctDNA in metastatic melanoma patients receiving treatment with PD1 inhibitors is an accurate predictor of tumour response, PFS and OS. Patients who had a persistently elevated ctDNA on therapy had a poor prognosis, and this may guide combination and sequencing of subsequent therapies.

Clearly, per the results of this study, patients did best when their circulating tumor DNA became undetectable under treatment.  Conversely, as one might suspect, when ctDNA remained elevated despite treatment, folks did less well...even when researchers controlled for known prognostic indicators like LDH, disease volume, etc.

We KNOW these facts.  We HAVE the technical ability.  WHY is this not standard of care??

Hang in there, ratties.  love, c

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