Dr. Stephen V. Liu interviewed by
Oncology Frontier at the 2023 WCLC conference.
Oncology Frontier: Could you talk about the significance of the results of Imbrella A Extension Study in SCLC ?
Dr. Liu: The Imbrella A extension study was a continuation of the IMpower133 trial, which is a phase III study for first-line extensive stage small cell lung cancer. That study, which was presented at the World Lung Meeting in 2018, showed the addition of immunotherapy to chemotherapy improved survival. Our report with the Imbrella extension is the five-year survival rate of patients treated with first-line atezolizumab plus carboplatin/etoposide. We showed the five-year survival rate was 12%. Although 12% is maybe not as high as we would like, it is clearly better than we had with historical five-year rates of survival of around 2%. With 12% of patients alive at the five-year mark, there really seems to be a plateau of survival.
Oncology Frontier: Does MD Anderson Cancer Center SCLC subtype have an impact on the treatment outcome of SCLC patients in Imbrella A Extension Study ?
Dr. Liu: The transcriptional subtypes that we get with small cell lung cancer define a different biology. There is a lot of heterogeneity within small cell lung cancer, and these subtypes are classified by expression of certain transcriptional factors, like NEUROD1, ASCL1 and POU2F3, or this inflamed subtype, really do define different biologic subsets of small cell lung cancer. What we don’t know is how to use those in practice. When we look at the IMpower133 Imbrella A extension, we can see they are not useful in determining who will be a long-term survivor. We see long-term survivors in all of those groups, but not the POU2F3, where the numbers overall are pretty small (that is the least common subtype). The inflamed gene signature does seem to predict benefit, but is not useful in predicting long-term survival. These are clearly real factors that differentiate subsets, but we just don’t know how to use them in the clinic. There are a lot of barriers right now. As of today, I would say we should not use any of those biomarkers to deprive someone of immunotherapy. The current approach is immunotherapy for everybody with extensive stage small cell lung cancer.
Oncology Frontier: What are the next treatments for SCLC patients who have progressed in first-line therapy in Imbrella A Extension Study? How can clinicians improve their chances of receiving second-line treatment ?
Dr. Liu: We want
long-term survival for everyone, but if we can only achieve it in a subset of
patients, what do we do with the patients who don’t achieve a long-term durable
response to chemoimmunotherapy? Our current second-line approved option in the
United States are lurbinectedin, a chemotherapeutic agent, or topotecan. There are many other promising agents
coming along. Those that are most promising are the bispecifics and the
bispecific T-cell engagers, like those targeting DLL3. There is a lot of
promise with tarlatamab. We will hear about one from Boehringer Ingelheim (BI) later at this meeting. These are
showing encouraging response rates and encouraging durability. We are also
hearing a lot about antibody drug conjugates (ADCs) and I-Dxd targeting B7-H3.
That is being presented at this meeting as well. The key here though is close
observation, because we do see late progression of small cell lung cancer. This
is not a disease where we see patients once or twice a year - we need close
follow-up, and educated patients understand what symptoms to recognize and when
to seek medical attention.
Oncology Frontier: In addition to the progress in immunotherapy, what other SCLC treatment areas are you interested in ?
Dr. Liu: For small cell
lung cancer, I think immunotherapy has a lot of promise because it offers the
potential for durability and long-term survival. Some of the newer agents, such
as the antibody drug conjugates, are showing a lot of encouraging early responses,
if we could figure out how to use them and incorporate that somehow with
immunotherapy for the potential synergy with these therapies. We are also
seeing that good old-fashioned treatments like radiation can be incorporated in
the extensive stage in the form of thoracic consolidative radiation therapy
along with chemoimmunotherapy. So stay tuned. Hopefully, we should have those
results pretty soon.