Weeks 169-171: s#!% hits the fan

Written by Lars Haakon Soraas

Weeks 169, 170 and 171 in the war on lung cancer have passed. Things could have been a lot better. Here are highlights (or maybe we should call them lowlights…):

  • After finishing the planned radiation of the cancerous lymph node conglomerate in the right hilum and another small lung metastasis, we travelled to Singapore for a holiday. We have been continuing to measure the tumor marker CEA in Singapore and, unfortunately, it has, despite the radiation, kept increasing rapidly.
  • We then traveled to Penang, Malaysia, where we now have stayed a week. Landing at the airport here, we coincidentally discovered two enlarged lymph nodes above Dyanne’s right collar bone. The location is pretty much exactly the same as the enlarged lymph node that got Dyanne diagnosed back in 2015. We thus got very worried.
  • This promoted us to do a PET-CT scan at a local hospital here in Penang. The scan results unfortunately shows activity in several places: the lymph nodes we had discovered above the right collar bone, some other lymph nodes, the primary tumor in the right lung, around a dozen places i the bones and one place in the liver. Although one should interpret such scans with caution, in particular since it was done at a different hospital than previous scans and there thus was limited opportunity to compare the new scan with older scans, it unfortunately seems there is progression. Maybe what is lighting up in the bones is not growing cancer, and maybe even the area that lights up in the liver is caused by something more benign than cancer. However, the lymph nodes and the primary tumor lighting up again seems to be difficult to believe is anything else than cancer.
  • We this past week also got the results from the testing done by Cegat GmbH on the tissue from the biopsy that was done a few weeks ago. They have made the following findings:
    • The original EGFR mutation (an exon 19 deletion) is still there, but the other EGFR mutation that previously has been found, T790M, is now gone.
    • Two other mutations which were also found in a biopsy done in August 2015, a mutation in the TP53 gene (V272L) and a mutation in the PTEN gene was also found (the mutation basically inactivates the gene).
    • In addition a mutation in the PIK3CA gene (E542) was found.
    • And a mutation in the RB1 gene (a homozygous deletion) was also found.
    • Another intriguing finding a high level of chromosomal instability.
    • Cegat also reported that the tumor mutation burden is low (2.2 variants/megabase).
  • I won’t comment extensively on each of the findings in the report, but will say that the combination of a TP53 mutation and RB1 loss is a sign of “small cell transformation”. Small cell transformation basically means that the cancer transforms from “non-small cell” to “small cell”. Which basically would be bad news. The good news is that the pathologist who has looked at the biopsy sample only sees “non-small cell” adenocarcinoma cells, and no “small cell” cancer cells. The PIK3CA mutation is potentially interesting because drugs targeting it are under development.
  • Despite all this bad news, Dyanne has been in pretty good shape the last few weeks and we have managed to enjoy our holiday here at least a bit.

In case anyone is interested, here is a table summarizing the genetic variants identified by Cegat in the most recent tumor sample from Dyanne.

Genetic alterations identified by Cegat in most recent tumor sample.

We are currently looking into what consequences all of this should have on Dyanne’s treatment. There seems little doubt that the systemic treatment needs to change. But how and to what are still very much work in progress. One treatment regime we are looking into is the quadruplet treatment that was tested in the IMpower150 trial. The quadruplet consists of a chemotherapy doublet (carboplatin and paclitaxel), atezolizumab (an immunotherapy drug) and bevacizumab (also known as Avastin). Results from the IMpower150 study have been presented at various conferences and the unique thing about this trial is that it is the only immunotherapy trial which has reported that also patients with EGFR mutations have benefited. While we were in Singapore, I attended ESMO Asia, a cancer conference, and at this conference detailed results on outcomes for the EGFR mutant patients in the IMpower150 study were presented. The results look promising. However, the many caveats with this kind of unplanned subgroup analysis, as well as the relatively small number of patients with EGFR mutations in the study, were highlighted by a discussant who reviewed the data. Furthermore, this quadruplet drug regime is rather toxic and whether it would be possible to get it implemented is another question. We will investigate this, and also other options, further before any decisions are made.

The war rages on.

Dyanne and butterfly. Entopia (butterfly farm), Penang, Malaysia

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