Afshin Dowlati, MD

Afshin Dowlati, MD, Lucile and Robert H Gries Endowed director, Center for Cancer Drug Development, University Hospitals, director Thoracic Oncology Program, UH Seidman Cancer Center, and professor, Department of Medicine Division of Hematology and Oncology, School of Medicine, discusses treatment decision-making for patients with late-stage small cell lung cancer (SCLC).

Multiple factors should be considered when selecting treatment for patients with late-stage SCLC, says Dowlati. The most important factor is their performance status, but whether or not the patient can tolerate chemotherapy and a combination regimen is also key.

Probably the most important factor in deciding treatment is really the performance status of the patient. We know that patients with small cell lung cancer even when they have a very poor performance, that combination chemotherapy can be effective in them as well. And many of them will have an improved performance status within 1 cycle of chemotherapy.

 It is not uncommon for patients to be admitted for their first cycle of chemotherapy and in that case, I give the chemotherapy alone and add the immunotherapy checkpoint inhibitors such as durvalumab [Imfinzi] with cycle number 2. For those that are fit and are in good performance status, I tend to use the addition of durvalumab with the chemotherapy upfront starting from cycle number 1.

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Afshin Dowlati, MD, discusses treatment decision-making for patients with late-stage small cell lung cancer.



Selecting Treatment for Late-Stage SCLC

Afshin Dowlati, MD, professor in the department of medicine and hematology at Case Western Reserve University and associate director for clinical research at Case Comprehensive Cancer Center, discusses the targeted therapies available for patients with 

-mutated late-stage non–small cell lung cancer (NSCLC).

According to Dowlati, the first choice for treating patients who have an 

 mutation in late-stage NSCLC is osimertinib (Tagrisso), which was approved based on the phase 3 FLAURA trial (NCT02296125) for patients with metastatic NSCLC with the more common exon 19 deletions or exon 21 L858R mutations. Osimertinib was also approved for the adjuvant setting after surgery for patients with earlier-stage disease with these mutations based on the ADAURA trial (NCT02511106).

Another agent, afatinib (Gilotrif), may be used in the frontline for patients with metastatic disease for the non-resistant 

 mutations S768I, L861Q, and/or G719X based on subset analysis of patients with durable responses with these mutations in the LUX-Lung 2 (NCT00525148), LUX-Lung 3 (NCT00949650), and LUX-Lung 6 (NCT01121393) trials.

Two other oral agents have shown efficacy in patients with 

 exon 20 insertions, Dowlati says. Amivantamab-vmjw (Rybrevant) was approved for the first line based on the phase 1 CHRYSALIS study (NCT02609776) of patients who had progressed on platinum-based chemotherapy. Mobocertinib (Exkivity) was approved based on a phase 1/2 study (NCT02716116) of patients with locally advanced or metastatic NSCLC who had progressed on platinum-based chemotherapy.

 Our agent of choice in the frontline setting of 

 mutations in the setting of stage IV disease, of course, is osimertinib, and that is based on randomized phase 3 clinical trials. Similarly, if we find an 

 mutation in early-stage disease, for which the patient had surgery, osimertinib has been approved for the adjuvant treatment of these patients as well. So really, at the end of the day, our main treatment strategy is with osimertinib.

Every once in a while, we have considered the use of afatinib for patients with uncommon 

 mutations, where there is some data on the use of afatinib for these specific, less common mutations. And for exon 20 insertion mutations within 

, 2 new agents have been approved for that setting as well. Mainly, amivantamab and [mobocertinib], another oral agent; they both have been approved for exon 20 insertion. So for the more common 

 mutations, exon 19, and exon 21, osimertinib is our drug of choice. For exon 20 insertion mutations, amivantamab is a drug that we have been using. And for less common 

Afshin Dowlati, MD, discusses the targeted therapies available for patients with EGFR-mutated late-stage non–small cell lung cancer.

Afshin Dowlati, MD | Authors

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Selecting Treatment for Late-Stage SCLC

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