What happen when first-line treatment fails?
In advanced or metastatic breast cancer, first-line treatment will fail after certain duration of time.
This is because cancer cells developed resistance to the treatment and not because the treatment is ineffective.
Life doesn’t end when first-line treatment fails.
We just continue fighting the cancer with other effective second-line and subsequent-lines treatments and the results can be seen from the improvement in average/ median overall survival.
Let’s go through HER2-targeted treatment after failure of first line HER2-targeting agents.
Second line setting
1. EGF100151 trial: Lapatinib + capecitabine vs capecitabine alone (CE Geyer, 2006)
- PFS: 8.4 vs 4.4 months in the combination and monotherapy group, respectively.
- Treatment was well tolerated despite being a combination therapy.
2. EMILIA study: T-DM1 vs lapatinib + capecitabine (S Verma, 2012)
- PFS: 9.6 vs 6.4 months, for T-DM1 and lapatinib plus capecitabine, respectively
- OS: 30.9 vs 25.1 months
- Suitable for patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane.
3. GBG 26/BIG 3-05 phase III study:
PFS: Patients who continued/restarted anti-HER2 treatment (trastuzumab or lapatinib) after 2nd progression (N=52) had a post-progression survival of 18.8 compared with 13.3months for those who did not receive 3rd line treatment with anti-HER2 agents (N=88) (HR 0.63; p=0.02).
Average/ median OS: Median overall survival was 20.6 and 24.9months with X and XH, respectively (HR=0.94 [0.65-1.35]; p=0.73)
Third line setting and beyond (heavily pre-treated)
TH3RESA study: T-DM1 vs treatment of physician’s choice (chemotherapy, hormonal therapy) (IE Krop, 2017)
- No PFS reported? Hm, suspicious. Anyway, when read in depth, it was reported that the median/ average duration of treatment was 5.2 vs 2.8 months, which is indirectly the PFS.
- Average/ median OS: 22.7 vs 15.8 months
- How can one live more than 20 months when the disease progressed with the above treatment after just 5 months? It’s with subsequent treatments! As long as there is treatment available, go for it.
EGF104900 trial: oral lapatinib + trastuzumab vs lapatinib alone in heavily pre-treated cohorts.
- PFS: 2.6 vs 1.9 months
- Average/ median OS: 14 vs 9.5 months
- Although the efficacy is not long, good effort by clinicians conducting this study nevertheless for offering patients further treatment options.
If you can’t afford expensive treatment such as with T-DM1, trastuzumab or lapatinib, other therapies such as palliative chemotherapy, hormonal therapy, radiotherapy and clinical trials are valid options.
I must stressed that treatment are more expensive and less effective when nearer to the end of life.
However, any proven therapies are better than no therapy at all, whether to reduce/ delay unpleasant symptoms or to prolong life.
My hopes are that my patients able to fulfil their wishes (eg. to see their children graduate, celebrate anniversary, etc) and to leave comfortably with dignity in the end.