Providing an update on evidenced-based management of small-cell lung cancer (SCLC) to an audience of medical oncologists at Roche’s Lung Day 2019, Professor Michael Millward, Foundation Chair of the Clinical Cancer Research at the University of Western Australia prefers to look at things from a ‘glass half full’ perspective. “We’ve been so limited in our management options for some time now. But finally we are starting to see some progress,” he began.
SCLC continues to pose challenges for oncologists
“It’s an uncommon disease, with a substantial unmet need,” emphasised Prof. Millward. “We’ve struggled to find effective, tolerable targeted therapies and at the moment we’re still reliant on chemotherapy in the first and second-lines.1 In the relapsed setting, data on immune-oncology (IO) therapies didn’t improve response rates or survival in CheckMate 331,2 or as maintenance therapy in CheckMate 451.3 Afterall, there is generally low programmed death-ligand 1 (PD-L1) expression on the tumour cells than we see in non-small cell disease.4 But that’s just the glass half-empty perspective.”
Recent data offers hope we could finally start to take back some control over SCLC
Prof. Millward presented data using IO in the frontline setting from IMPOWER 133 and CASPIAN. “Looking at these studies it is amazing how strikingly similar the overall survival (OS) curves are.5,6 They’re almost super-imposable.5,6 This is really promising as we rarely see results from two studies – even in the same patient population – so similar. We see a divergence in the curves around 6 months,5,6 which can’t just be due to maintenance therapy alone as CheckMate 451 debunks that myth,”3 he noted.
However, progress remains slow on the biomarker front with the historical challenges of tumour biomarker analysis persisting in the latest trials. “Even in IMpower 133, enough evaluable tissue for analysis was only obtained in one third of patients.5 It’s a tricky disease to biopsy. The pathology is usually sheets of small cells with areas of necrosis7. You don’t often get large biopsies. So this has slowed progress in this area,” explained Prof. Millward. Of those samples available for analysis from IMpower 133 and CASPIAN, Prof. Millward explained how neither “PD-L1 nor blood tumour mutational burden (bTMB) were predictive of response or outcome.”5,6
Where to now? How to innovate in SCLC
To close the session, Prof. Millward provided commentary on what we should be looking for to classify a treatment as truly practice-changing in this space. “It’s such a hard one to innovate given everything we’ve spoken about so far. So how does the research stack up in the SCLC space?” Here’s the criteria Prof. Millward’s took the audience through to evaluate IO in the frontline setting:
| Criteria | Prof. Millward’s case |
| Does the study compare the new treatment vs standard of care? | “Both IMpower 133 and CASPIAN* compared frontline treatment to the current standard of care” |
| Research population reflects clinical practice? | “Perhaps. Recruitment in the trials allowed brain metastases” |
| New treatment offers significant, clinically-meaningful outcomes? | “Yes, we saw a benefit above the standard of care in both trials” |
| Results are reproducible? | “The similarity of results between the trials is very reassuring” |
| Cost of treatment is reasonable? | “Here’s where more work needs to be done” |
In concluding, Prof. Millward reminded the audience of the work that still needs to be done. “There’s results from KEYNOTE 604**, data on the role of upfront radiation therapy and consideration of the immunosuppressive microenvironment that all warrant our attention.”
*The regimen used in the CASPIAN trial is not TGA approved.
**The regimen used in KEYNOTE 604 is not TGA approved.
This article was sponsored by Roche, which has no control over editorial content. The content is entirely independent and based on published studies and experts’ opinions, the views expressed are not necessarily those of Roche.
References
- Yang S et al. J Hematol Oncol 2019;12:47.
- Reck M et al. Efficacy and safety of nivolumab (nivo) monotherapy versus chemotherapy (chemo) in recurrent small cell lung cancer (SCLC): Results from CheckMate 331. ESMO Immuno-Oncology Congress 2018 in Geneva, Switzerland. LBA5.
- Owonikoko T et al. Nivolumab (nivo) plus ipilimumab (ipi), nivo, or placebo (pbo) as maintenance therapy in patients (pts) with extensive disease small cell lung cancer (ED-SCLC) after first-line (1L) platinum-based chemotherapy (chemo): Results from the double-blind, randomized phase III CheckMate 451 study. Ann Oncol 2019; 30(Suppl 2). LBA-1_PR.
- Pavan I et al. J Immunother Cancer 2019;7:205.
- Horn L et al. N Engl J Med 2018;379:2220-2229.
- Paz-Ares L et al. Lancet 2019;S0140-6736(19)32222-6.
- Karachaliou N et al. Transl Lung Cancer Res 2016;5(1):2-15.