Improving Overall Survival In Extensive Stage Small Cell Lung Cancer - Episode 4

A Detailed Conversation on Treatment of SCLC

Jyoti D. Patel, MD:Small cell lung cancer accounts for 13% to 15% of all lung cancer diagnoses. By definition, it’s considered an orphan cancer because it’s less common. It is an area in which there has been tremendous need to improve outcomes. Historically, therapies were platinum and etoposide given for 4 to 6 cycles. There have been significant efforts to improve outcomes. For example, intensification of therapy. Several decades ago, we even looked at doing transplant in this population of patients. Unfortunately, this is a cancer for which relapse is common, even though we see a significant response rate and significant improvement in symptomatic burden of disease with response rates of 70% to even 80% for many patients. This cancer is one that can be relentless and can relapse quite quickly.

Efforts have looked at giving multiple agents. For example, intensification. It has looked at stem cell transplant. Therapies that have also been looked at are the addition of longer therapies, or switch maintenance, or continuation maintenance for these drugs. With carboplatin-etoposide, these drugs tend to be quite myelosuppressive. Subsequent therapy can sometimes pose challenges. Bringing drugs like topotecan earlier to maintenance has proven to be ineffective.

If we look at what’s happened in the past decades, we can think of at least 60 phase III trials that have been negative in small cell lung cancer in early disease. And that’s using different oral agents, different VEGF inhibitors, 2 versus 3 drugs. We really haven’t made significant impact. What we’ve seen is that response rates might be higher. That progression-free survival—you’re better in giving continuation therapy, but there has been very little impact in overall survival.

Efforts that have improved overall survival include radiation for some sets of patients—for example, chest RT [radiation therapy]. That comes with toxicity, and there is variable uptake among centers who would be appropriate for chest RT. Then we felt that PCI [prophylactic cranial irradiation] could improve survival in patients with extensive-stage disease. Later confirmatory trials from Japan demonstrated no improvement in OS [overall survival] but perhaps a change in PFS [progression-free survival].

In both the CASPIAN and IMpower133 trials, we see that overall survival is improved. Look at progression-free-survival. There’s not a significant improvement or such a large delta in that space. It’s a smaller hazard ratio. We talk about response rates with immunotherapy and chemotherapy not being significantly higher than with chemotherapy alone. Again, this is a cancer that tends to be chemotherapy responsive.

When we talk to a patient about what treatment looks like and sort of begin that journey for what therapy will be like over the next months, 1 thing we communicate very early on is that this is a difficult cancer and that therapy will likely be ongoing. There may be periods when we take treatment breaks, but this is a cancer in which relapse is common.

I think we would talk about these 2 phase II trials, and there’s clear evidence that immunotherapy improves outcomes. Although the difference in overall survival is modest—less than 3 months—I can say very clearly that the proportion of patients who are alive and have minimal burden of disease at 12 and 18 months is significantly better with immunotherapy. I think that’s important to communicate to patients.

Even though the PFS doesn’t look much different, if we look at the number of patients who have recurrent disease or progressive disease, that’s less. Moreover, the addition of immunotherapy to chemotherapy does not increase toxicity. It’s well tolerated. And so this idea of more therapy or intensification with 3 drugs makes good sense. There’s a chance this patient could live longer. There’s a chance that this patient could really benefit from up-front immunotherapy and develop stable disease at 12 to 18 months to get to those milestones that are important for her without a risk of significantly increased toxicity.

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