Treatment Approach in Limited- and Extensive-Stage SCLC

Jyoti D. Patel, MD:About a third of the people we meet at diagnosis have limited-stage disease or disease that’s confined within a hemithorax. The rest of the patients have more extensive-stage disease, with disease outside the chest—predominantly the bones, liver, adrenal glands, and brain. For patients with limited-stage disease, their disease is felt to be potentially curable. The approach to therapy is a combination of chemotherapy and radiation. Radiation can either be once-daily for 6 weeks, or there are data supporting twice-daily radiation. There’s biologic rationale for that.

The American trial that’s looking at these 2 different radiation approaches continues to accrue. An English trial that has been reported showed no difference. So we await confirmatory data. Generally, for patients who are very motivated, I recommend twice-daily radiation. If we can do that with the family and transportation, I tend to do that off trial.

For patients with limited-stage disease, we also have evidence that prophylactic cranial irradiation [PCI] improved survival. Certainly given the disparate results in patients with extensive-stage disease, there are trials planned, exploring the use of PCI in both the limited-stage and extensive-stage populations to see whether CTs [computed tomography scans] or MRI [magnetic resonance imaging] surveillance are reasonable options.

For most patients, though, or for those patients with extensive-stage disease, chemotherapy is the initial treatment. Again, that’s palliative therapy. We know that without treatment, patients with extensive-stage disease generally live on the order of months—between 3 and 6 months. When we do plain chemotherapy with a backbone of platinum and etoposide, we think about survival. The survival that has been shown in recent trials is around 10 months.

We know that a great number of patients will have progressive disease within 3 months. For those patients, we consider second-line therapy. There is another cohort of patients with refractory disease at the get-go, who never have a response or who have progressive disease within 45 days of treatment. Those patients have less of a response to second-line therapy. In those patients who do quite well for 6 months or so, who have long responses to chemotherapy, we will often retreat with cisplatin and etoposide.

In the relatively recent past, we’ve now incorporated immunotherapies. There have been 2 large trials that have demonstrated improvements with immunotherapy and chemotherapy, and I think we now have a better frontline standard for our patients. That’s really what I talked to our patient about, who is so well, as a treatment approach.

Often, for patients who are diagnosed with small cell lung cancer, we find out pretty early whether it’s a histological diagnosis. Unlike non—small cell lung cancer, where we wait for a number of different molecular tests or PD-L1 [programmed death-ligand 1], in small cell lung cancer that has been less relevant so far. Often, we’re unable to do it because cells tend to be necrotic. But we have been able to capture TMB [tumor mutational burden] and PD-L1 information in about a third of patients on clinical trials.

Thus far, those parameters have not been helpful. There’s no biomarker that has been very helpful for selecting therapy in the frontline setting, and I’ll talk about that in the paradigm of immunotherapy in just a minute. But we generally don’t do molecular testing unless it’s part of a research effort. We know there are ubiquitous mutations inP53andRB, but beyond that, we haven’t been able to really detect actionable mutations. And so I don’t generally get tumor mutational burden. I don’t do genetic testing, nor do I do PD-L1 for my patients with small cell lung cancer.

Transcript edited for clarity.

Case: A 73-Year-Old Female With Stage IV SCLC

Initial presentation

• A 73-year—old woman presented with shortness of breath, productive cough, chest pain, fatigue, anorexia and an 18-lb weight loss.
• PMH: HTN
• SH: Elementary school teacher; 50 pack year smoking history; quit 6 years ago; married with 2 children and her first grandchild on the way.
• PE: Dullness to percussion, decreased breath sounds, BMI 17

Clinical workup

• Imaging:
  • Chest x-ray showed a hilar mass and a 5.4cm right lower lobe mass
  • Chest/abdomen/pelvic CT scan revealed mediastinal adenopathy, right lower lung lobe mass, suspicious liver lesions
  • PET scan showed activity in the left upper lobe mass and supraclavicular nodal areas and liver lesions
  • No metastases to brain on MRI
• IR biopsy of liver revealed small cell lung cancer
• Staging: T3N3M1 - IVb
• ECOG PS 1

Treatment

• Concurrent durvalumab with carboplatin/etoposide; has completed 4 cycles
• Developed constipation and nausea after second cycle (constipation successfully treated with increased oral hydration and docusate; nausea treated with ondansetron)
• Repeated chest/abdomen/pelvis CT with contrast after every 2 cycles demonstrated significant response. After 4 cycles patient started maintenance durvalumab for 6 months
• Continued durvalumab every 4 weeks, with CT scans at 3 and 6 months