Imagine the following scenario: A User using Lotus Notes Client sends a mail to an user who is using Outlook/MS Exchange 2003. Furthermore, this mail is routed via SMTP and not over a Notes Connector. In this scenario, the received mail has an attached .ics-File instead of being displayed as a regular Outlook-Appointment (see Screenshot below)  

Therefore, the user can not answer the invitation. Luckily, Microsoft has released an Exchange-Hotfix (2003 only) to remedy this behaviour. It has the KB Number KB948451, and seems to be a private HF, meaning that you have to call Microsoft PSS to get the fix (there's not even a KB on support.microsoft.com for this yet). The fix includes the following files and versions:

6.5.7654.0 1135616 2008/06/27 21:22:18 davex.dll
6.5.7233.41 31744 2005/08/08 22:02:44 exhotfix.dll
6.5.7233.41 13824 2005/08/08 22:02:44 exhotfixuninst.dll
6.5.7654.0 2623488 2008/06/27 21:22:21 exoledb.dll
6.5.7654.0 70144 2008/06/27 21:12:45 exosal.dll
6.5.7233.41 8192 2005/08/08 22:02:44 exspmsg.dll
6.5.7654.0 3381248 2008/06/27 18:59:22 mdbmsg.dll
6.1.22.4 209632 2005/03/03 21:51:17 spuninst.exe
6.5.7654.0 5266944 2008/06/27 21:14:15 store.exe

As IMail conversion runs on the backend, it should theoretically be enough to install it on the backend. As best practice, try to have your backends/frontends/connectors/etc. on the same patchlevel.

After installing the Hotfix, new invitations look more like standard Outlook-Appointmens (see screenshot below): 

As you can see, users now have the typical buttons (Accept, Reject, Propose new time) in the header row.

Hope this helps someone