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ROS1+ Cancer Treatment other than Targeted Therapies

Targeted therapy drugs are the preferred first-line treatment for metastatic ROS1+ NSCLC. However, when targeted therapy is not available or stops being effective, ROS1 clinicians turn to other cancer treatments. The following is a discussion of the other types of treatments for ROS1+ cancer. 


Chemotherapy and ROS1+ cancer

Chemotherapy drugs (especially pemetrexed alone or in combination with carboplatin)  can be effective against ROS1+ cancers and are sometimes used by ROS1 Clinician-Researchers when TKIs cease to be effective or when appropriate TKIs are not available.


A 2016 study compared how well pemetrexed-based chemotherapy worked for lung cancers driven by gene alterations (EGFR, ALK, KRAS, ROS1) in East Asian people. It found patients whose cancer had ROS1 fusions had a better overall response rate, disease control rate, and progression-free survival than people with other gene alterations . Nearly 60% of ROS1+ cancer patients responded, and nearly 90% experienced cancer shrinkage or stability.


Although targeted therapy drugs are the preferred first-line treatment for ROS1+ cancer, patients may benefit from pemetrexed-based chemotherapy when targeted therapy drugs are not available.


Radiation or surgery

In situations where the progression of cancer is limited in extent, it may be possible to stay on a targeted therapy drug and treat the area of progression with focused radiation, some other form of ablation, or even surgery.


A 2014 study of anaplastic lymphoma kinase-positive NSCLC patients taking crizotinib found that “stereotactic radiation therapy can safely and durably control sites of extra-central nervous system oligoprogressive disease.” A 2022 study found “Local therapy for progression on ALK, ROS1, or RET TKIs is associated with clinically meaningful time on continued TKI therapy beyond progression, especially earlier in the course of disease.” A randomized clinical trial in EGFR+ NSCLC patients in China found the addition of stereotactic body radiation for patients taking EGFR targeted therapies “delayed the onset of acquired resistance to EGFR-TKIs and prolonged the [progression free survival] and [overall survival] of patients.”


Targeted therapy combinations

Targeted therapy combination therapies are being explored in clinical trials in an attempt to prevent the development of off-target acquired resistance or to address cancers that have developed a second driving mutation (ALK, EGFR, RET, MET, etc.). However, targeted therapy combinations can be more toxic, so caution must be taken when considering targeted therapy combinations.


Immunotherapy for metastatic ROS1+ cancer

Immunotherapy should NOT be used as first-line treatment in metastatic (stage 4) ROS1+ cancer because (1) it will likely be ineffective, and (2) it may delay or prevent later use of targeted therapy. Immune checkpoint inhibitors (ICIs, or immunotherapy) should only be used for metastatic ROS1+ cancer after targeted therapy and chemotherapy options have been exhausted. 


Note that treatment guidelines for lung cancer that is CURABLE (stages I, II, and III) do recommend use of immune checkpoint inhibitors.


Clinical trials are exploring whether a different type of immunotherapy called autologous tumor-infiltrating lymphocyte (TIL) therapy may be useful for patients with oncogene-driven NSCLC.


Clinical trials for ROS1+ cancer

A clinical trial may also be a good treatment option for a patient with ROS1+ cancer as first, second, or later line of treatment. A clinical trial may be attractive for patients with no access to approved ROS1 TKIs, especially if it provides access to a TKI that has been approved in other countries. Learn more about participating in a clinical trial and explore which ROS1 TKI clinical trials are available.


Fortunately, research about the effective treatment of ROS1+ cancer is evolving. The ROS1ders strive to help patients stay in touch as new treatment discoveries are made.  


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